|Year : 2016 | Volume
| Issue : 5 | Page : 716-722
Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis
Nan Li1, Chris KC Wong2, C Yan Cheng1
1 The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York 10065, USA
2 Department of Biology, Hong Kong Baptist University, Hong Kong, China
|Date of Submission||02-Jul-2015|
|Date of Decision||27-Jul-2015|
|Date of Acceptance||26-Aug-2015|
|Date of Web Publication||20-Nov-2015|
C Yan Cheng
The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York 10065
Source of Support: None, Conflict of Interest: None
Plastins are a family of actin binding proteins (ABPs) known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins also support cell movement in response to changes in environment, involved in cell/tissue growth and development. They also confer plasticity to cells and tissues in response to infection or other pathological conditions (e.g., inflammation). In the testis, the cell-cell anchoring junction unique to the testis that is found at the Sertoli cell-cell interface at the blood-testis barrier (BTB) and at the Sertoli-spermatid (e.g., 8-19 spermatids in the rat testis) is the basal and the apical ectoplasmic specialization (ES), respectively. The ES is an F-actin-rich anchoring junction constituted most notably by actin microfilament bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded some insightful information regarding the mechanism by which plastin 3 regulates the status of actin microfilament bundles at the ES via its intrinsic actin filament bundling activity. Herein, we provide a brief review on the role of plastins in the testis in light of this report, which together with recent findings in the field, we propose a likely model by which plastins regulate ES function during the epithelial cycle of spermatogenesis via their intrinsic activity on actin microfilament organization in the rat testis.
Keywords: actin binding proteins; actin bundling proteins; cytoskeleton; F-actin; fimbrins; plastins; seminiferous epithelial cycle; spermatogenesis; testis
|How to cite this article:|
Li N, Wong CK, Cheng C Y. Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis. Asian J Androl 2016;18:716-22
|How to cite this URL:|
Li N, Wong CK, Cheng C Y. Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis. Asian J Androl [serial online] 2016 [cited 2022 Nov 28];18:716-22. Available from: https://www.ajandrology.com/text.asp?2016/18/5/716/166583
| Introduction|| |
Plastins are a family of actin binding proteins (ABPs) having the intrinsic activity of conferring actin microfilament bundling, promoting long stretches of microfilaments with the same polarity to be bundled. ,,,, This actin bundling capability of a single plastin polypeptide is mediated by the two tandem pairs of CH (calponin homology) domain in its polypeptide sequence creating two ~27 kDa actin binding domains (ABD1 and ABD2) ([Figure 1]) that are being used to create actin microfilament bundles, such as those found in the ectoplasmic specialization (ES) at the Sertoli-Sertoli and Sertoli-spermatid interface in the mammalian testis, which are also essential to confer Sertoli cell and spermatid adhesion, polarity and spermatid transport. ,, The N-terminal region of plastin contains a calcium ion-binding domain (CaBD) composed of two EF hand motifs  ([Figure 1]). The first member of the plastin ABP family found in vertebrates is plastin 1 (also known as I-plastin or intestine plastin) ([Table 1] and [Figure 1]). It was first identified in 1979 in microvilli from intestinal brush border of chicken as a 68 kDa polypeptide, shown to be involved in the organization of actin microfilament bundles to constitute the microvillus core filaments,  and subsequently shown to be expressed by cells of the colon, and kidney, besides small intestine in humans.  It was also called fimbrin as it was found to associate with other cell surface structures such as focal adhesions, microspikes and membrane ruffles, besides microvilli, in fibroblasts and mammary cells in studies in vitro.  Fimbrin was subsequently shown to bind and cross-link actin microfilaments, , thereby creating polarized actin microfilament bundles in mammalian cells to support cell polarity, cell adhesion, locomotion, and other cellular events. At about the same time, another 68 kDa protein called plastin 2 (also known as L-plastin) that confers actin microfilament bundles was found to be highly expressed in lymphocytes,  leukocytes  (i.e., hematopoietic cells), and also cancer cells such as transformed human fibroblasts, , also known as lymphocyte cytosolic protein 1 (LCP1) ([Table 1] and [Figure 1]). Plastin 2 is known to be involved in T-cell motility and activation,  and plastin 2 deficient neutrophils fail to kill bacterial pathogens  since these cells lack the ability to quickly rearrange their actin cytoskeleton in response to the pathogens. Plastin 3 (also known as T-plastin), also a 68 kDa monomeric polypeptide, is found in cells derived from solid tissues such as neurons, auditory hair cells, melanocytes, and osteoblasts ,,, ([Table 1] and [Figure 1]). Defects of plastin 3 in humans due to mutation are known to associate with osteoporosis, leading to bone fracture.  This is possibly due to defects in the organization of actin filament bundles in bone cells, perturbing the necessary conversion of mechanical signals to biochemical signals in osteoblasts and osteoclasts rapidly,  leading to osteoporosis.  Interestingly, a study of homozygous deletion of the survival motor neuron 1 (SMN1) gene that causes spinal muscular atrophy (SMA) - a genetic disorder leading to early childhood lethality - using both a mouse and a zebrafish model has shown that overexpression of plastin 3 can repair neuronal defects associated with the SMA disorders, such as the axon length and outgrowth defects, illustrating plastin 3 is a protective modifier of SMA.  Studies have shown that there is ~75% sequence similarity between all three plastins found in mouse and human , ([Table 2]), and the similarity of plastin 1, 2 and 3 between mouse and human proteins are of 94%, 97% and 99%, respectively, based on the homology analysis tools in BLAST (Basic Local Alignment Search Tool) from National Center for Biotechnology Information using corresponding protein sequence data of plastins in GenBank ([Table 2]). Interestingly, Sertoli cells More Details were found to express all three members of the plastin ABP protein family: plastin 1, 2 and 3, whereas germ cells expressed only plastin 1 and 2,  illustrating nature has installed multiple actin bundling proteins to protect the integrity of actin microfilament bundles at the ectoplasmic specialization (ES) to support cell adhesion function and spermiogenesis - the two essential functions of the ES. Thus, it is not surprising that mutation or deletion of either plastin 1,  2  or 3  in humans or mice did not seem to affect fertility since it is likely that the lost of one plastin can be superseded by the other two members of the family in the testis. Thus, it will be of interest to examine if a triple knockdown of all three plastins would affect fertility by impeding spermatogenesis. However, a recent report has shown that the knockdown (KD) of plastin 3 in Sertoli cells by RNAi indeed perturbs the organization of actin microfilaments in Sertoli cells and also the ES in the testis in studies of in vitro and in vivo, illustrating the functional significance of plastin 3 in spermatogenesis. Herein, we briefly describe these findings and critically evaluate the role of plastin 3 in the testis in light of findings in the field.
|Figure 1: Schematic illustration of the various common functional domains in members of the plastin protein family. (a) Plastin, such as plastin 2 (L-plastin) is known to have two putative phosphorylation sites (e.g., Ser-5 and -7) near its N-terminus. The phosphorylation of these sites is known to activate plastin 2 to unleash its intrinsic actin bundling activity, but similar phosphorylation site(s) in plastin 1 and 3 remains to be identified. It is followed by the two EF-hand, a helix-loop-helix structural domain (or motif), found in a large family of calcium-binding proteins, along with the nuclear export signal sequence. There are also two actin binding domains (ABDs) of ABD1 and ABD2, each is comprised of two in tandem calponin homology (CH) domains. (b) The binding of two actin microfilaments in each molecule of plastin thus induces actin microfilament bundling such as those found at the ES.|
Click here to view
| Plastins and The Testis|| |
In the mammalian testis, when the cross-section of a seminiferous tubule is examined microscopically, the seminiferous epithelium is notably divided into the adluminal (apical) and the basal compartment by the blood-testis barrier (BTB). Under electron microscope, the most prominent cell junction detected in the seminiferous epithelium of the adult rat testis is the ectoplasmic specialization (ES) first named in 1977 , at the Sertoli cell-cell interface at the BTB and at the Sertoli-spermatid interface, designated basal and apical ES, respectively, referring on their relative location in the seminiferous epithelium. While the morphological features and the possible physiological function of the ES are known for several decades, the mechanisms by which the ES regulates Sertoli and spermatid polarity, adhesion, and spermatid transport are beginning to emerge until recent years. ,,,, The ES, unlike other cell-cell anchoring junctions that also use F-actin for their attachment, is a testis-specific actin-rich anchoring junction. The apical ES anchors spermatids (steps 8-19) onto the Sertoli cell in the seminiferous epithelium, it is composed of only one array of actin filament bundles restricted to the Sertoli cell at the Sertoli cell-spermatid interface, and no corresponding ultrastructure is found in the spermatid ([Figure 2]). Furthermore, once apical ES appears in step 8 spermatids, it replaces all other junctions (e.g., gap junction and desmosome) and is the only anchoring device remaining throughout spermiogenesis. On the other hand, the basal ES, is restricted to the Sertoli cell-cell interface at the BTB, is formed by two arrays of actin filament bundles, each of which is found in one of the two adjacent Sertoli cells ([Figure 3]). Unlike apical ES, basal ES coexists with TJ and gap junction, which together with the intermediate filament-based desmosome create the BTB. At the ES, actin microfilaments that lie perpendicular to the Sertoli cell plasma membrane are sandwiched in-between cisternae of endoplasmic reticulum (ER) and the apposing Sertoli cell-spermatid (apical ES) ([Figure 2]) or Sertoli cell-cell (basal ES) plasma membrane ([Figure 3]). Due to the intrinsic actin bundling activity of plastins ([Figure 1]), it is conceivable that these ABPs are crucial for the assembly and regulation of actin microfilaments at the ES during the epithelial cycle. Surprisingly, it is almost four decades since the discovery of the first plastin namely plastin 1 (fimbrin), there are few published reports in the literature that examined the functional significance of plastins in the ES except an earlier study in 1989, which was almost 10 years after the initial discovery of plasmin 1 (fimbrin), that a frimbrin-like 83 kDa protein was identified in the SDS-extract of the ES from rodent testes by immunoblotting.  In this study, frimbrin and vinculin were detected in the SDS-extract of ES and suggested that fimbrin might be used to cross-link actin microfilaments at the ES to confer a unique testis anchoring junction.  Since then, no functional study can be found in the literature. In order to better understand the regulation of actin microfilaments at the ES, we recently report findings based on the use of plastin 3-specific siRNA duplexes by RNAi for its knockdown in Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimics the Sertoli cell BTB in vivo, as well as it knockdown in the testis in vivo.  Sertoli cell express all three plastins with plastin 3 being the predominant form, whereas total germ cells express plastin 1 and 2, but not plastin 3.  Plastin 3 also co-localizes with actin microfilaments in Sertoli cells.  The expression of plastin 3 in the seminiferous epithelium displays restrictive spatiotemporal pattern.  For instance, plastin 3 is expressed at the basal ES of the BTB in virtually all stages of the epithelial cycle but most prominently in stages V-VII tubules and considerably diminished in stage VIII tubules when the BTB undergoes remodeling/restructuring, perhaps being used to accommodate the transport of preleptotene spermatocytes across the barrier by modifying the organization of actin microfilament bundles at the basal ES.  At the apical ES, plastin 3 is expressed almost exclusively in stage VII tubules, localized restrictively to the tip of spermatid heads, co-localized with nectin-3,  which is a spermatid-specific apical ES protein that forms an adhesion protein complex with nectin-2 in Sertoli cells.  Following a knockdown of plastin 3 by RNAi in Sertoli cells cultured with an established functional TJ barrier, it was noted that actin microfilaments failed to align as bundles across the Sertoli cell cytosol, instead, they were mis-aligned across cell cytosol and some microfilaments were truncated with shorter stretches of filaments, but the vimentin-based intermediate filaments were unaffected in these cells.  This, in turn, failed to support proper localization of actin-based basal ES protein complexes, such as N-cadherin-β-catenin, since these proteins were found to be grossly internalized, re-distributed from near the cell surface to cell cytosol, thereby perturbing the Sertoli cell TJ-permeability barrier function.  Surprisingly, the localization of TJ-based protein complex, such as claudin-11/ZO-1, at the Sertoli cell surface was unaffected; this thus explains the partial maintenance of the Sertoli cell TJ barrier function following a mis-localization of basal ES proteins after plastin 3 knockdown.  These findings also suggest that other plastins found in the testis, such as plastin 1 and plastin 2 expressed by Sertoli cells, or other actin bundling proteins, such as ezrin,  palladin,  and Eps8  found in the testis may supersede the lost function of plastin 3. It is also noted that a knockdown of plastin 3 in Sertoli cells also impedes the proper localization of an actin barbed end capping and bundling protein Eps8, actin cross-linking and bundling protein palladin, as well as the branched actin polymerization protein Arp3.  The mis-localization of these other actin binding and regulatory proteins could also be the result of changes in the organization of actin microfilaments across the Sertoli cell following plastin 3 knockdown, so that they could no longer localize properly as found in normal Sertoli cells. Based on these findings, we now propose two hypothetical models by which plastin 3 regulates actin microfilament organization at the apical ([Figure 2]) versus basal ([Figure 3]) ES, facilitating endocytic vesicle-mediated protein trafficking. As such, "old" apical as well as "old" basal ES/BTB proteins can be endocytosed and recycled for the assembly of "new" apical and BTB proteins, respectively. These changes as depicted in [Figure 2] thus accommodate the release of fully developed elongated spermatids (i.e., spermatozoa) at spermiation, and the transport of preleptotene spermatocytes across the barrier at stage VIII as shown in [Figure 3]. It is conceivable that plastin 3 is not working alone, instead, it is working in concert with a number of structural and regulatory proteins that effectively organize actin microfilaments and also MT-based cytoskeleton for the transport of spermatids versus preleptotene spermatocytes ([Figure 2] and [Figure 3]).
|Figure 2: A hypothetical model illustrating the role of plastins in the remodeling of the apical ES during the epithelial cycle of spermatogenesis. The left panel is a schematic drawing of a stage VII tubule illustrating the apical ES is intact with functional adhesion protein complexes, such as nectin-afadin and integrin-laminin, utilizing F-actin as the attachment site to confer spermatid adhesion onto the Sertoli cell in the seminiferous epithelium in the adluminal (apical) compartment. The actin filament bundles are maintained by the actin bundling proteins such as plastin 3. From late stage VII through early stage VIII (middle panel), actin microfilaments are becoming unbundled, via the combined action of an up-regulation of the barbed end branched actin nucleation protein Arp2/3 complex/N-WASP that generate branched actin filaments, and a down-regulation of actin cross-linking and bundling protein plastin 3. This thus converts actin microfilaments from a bundled to a un-bundled/branched configuration, facilitating endocytic vesicle-mediated protein trafficking events of endocytosis, and recycling to assemble "new" apical ES derive from step 8 spermatids that arise in stage VIII tubules versus endosome-mediated protein degradation. These endocytic vesicle-mediated trafficking events are also facilitated by the presence of polarized microtubules (MTs) that serve as the track for the intracellular transport of these vesicles. In late stage VIII (right panel), the extensive degeneration of apical ES facilitates the release of fully developed spermatids (i.e., spermatozoa) at spermiation. At the same time (see right panel), elongating spermatids also develop progressively with intact apical ES.|
Click here to view
|Figure 3: A hypothetical model illustrating the role of plastins in the remodeling of the basal ES at the BTB during the epithelial cycle of spermatogenesis to facilitate the transport of preleptotene spermatocytes across the immunological barrier. Preleptotne spermatocytes transformed from type B spermatogonia that are detected at stage VII of the epithelial cycle are being transported across the BTB as shown in this schematic drawing, involving extensive remodeling of actin microfilament bundles at the basal ES. The left panel depicts the schematic drawing of a cross-section of the seminiferous epithelium in a stage VII tubule in which an intact BTB is located above the preleptotene spermatocyte (PLS). The BTB is composed of F-actin-based TJ (e.g., occludin, JAM-A, CAR, ZO-1), basal ES (N-cadherin, β-catenin, nectin-2, afadin), and GJ (gap junction) (e.g., connexin 43, connexin 33) proteins, as well as intermediate filament-based desmosome proteins (e.g., desmoglein-2, desmocollin-2). In late to early stage VIII (see middle panel), actin microfilament bundles in the "old" BTB above the PLS are becoming unbundled, via the combined action of an up-regulation of the barbed end branched actin nucleation protein Arp2/3 complex/N-WASP that generate branched actin filaments, and a down-regulation of actin cross-linking and bundling protein plastin 3, perhaps involving other actin bundling proteins such as ezrin, palladin, and fascin 1. This thus converts actin microfilaments from a bundled to an unbundled/branched configuration, facilitating endocytic vesicle-mediated protein trafficking events of endocytosis, and recycling so that a "new" BTB can be assembled behind the PLS. Other unwanted internalized "old" BTB proteins can also be subjected to endosome-mediated degradation. This timely sequence of "old" BTB breaks down versus "new" BTB reassembly thus facilitates the transport of PLS across the barrier until a "new" BTB is established as shown in the right panel when PLS has transformed to leptotene spermatocyte (LS) in early stage IX of the epithelial cycle.|
Click here to view
| Plastin 3 and Spermatogenesis|| |
When plastin 3 was silenced in the testis in vivo by RNAi, thereby perturbing the organization of actin microfilaments at the ES, the most obvious phenotypes found in the seminiferous epithelium were a distinctive failure of: (i) spermatid transport and (ii) phagosome transport.  For instance, elongated spermatids (e.g., step 19 spermatids) were found to be embedded deep inside the epithelium in stage VIII tubules, and some step 19 spermatids were also detected near the basement membrane even in stage X tubules and were present among step 10 spermatids,  illustrating a failure in spermatid transport at these stages. Interestingly, phagosomes derived from residual bodies engulfed by Sertoli cells that were found near the basement membrane in stage IX tubules in control testes  remained at the adluminal edge of the epithelium, in stage IX tubules after plastin 3 KD in the testis as of stage VIII tubules.  These findings thus confirm the concept that actin microfilament bundles at the ES maintained by plastins are being used to confer transport of spermatids and other organelles (e.g., phagosomes) during the epithelial cycle. The lack of significant impact on the status of spermatogenesis following specific KO of either plastin 1, 2 or 3 as noted in [Table 1] is likely that other plastins as well as other actin bundling proteins can supersede the loss of one of the plastin genes. This notion, in fact, is supported by observations on the actin microfilament organization in Sertoli cells following plastin 3 KD, since the silence of plastin 3 by ~70% using RNAi was found to induce extensive truncation of actin microfilaments in Sertoli cells, some branched actin microfilaments were notably detected, even though the localization of TJ-based adhesion protein complexes (e.g., claudin-11/ZO-1) remained relatively unaffected.  However, it is noted that mis-localization of basal ES proteins (e.g., N-cadherin/β-catenin) was grossly affected and perturbed.  In this context, it is of interest to note that while plastin 3 is important to confer actin bundles at the ES, it can also impede actin microfilament turnover because plastin is known to stabilize F-actin network in cells. , Thus, plastin is likely working in concert with cofilin, an actin depolymerization and severing protein  as well as the Arp2/3 complex  to affect spermatid and phagosome transport across the seminiferous epithelium during the epithelial cycle. This possibility must be carefully evaluated in future studies.
| Concluding Remarks and Future Perspectives|| |
As briefly discussed herein, plastins are a family of novel actin bundling proteins in which plastin 3 is recently shown to play a crucial role in maintaining the actin microfilament bundles in Sertoli cells, conferring the ES its ability to facilitate the transport of developing spermatids during spermiogenesis, and also other organelles (e.g., phagosomes) during the epithelial cycle of spermatogenesis. Based on the KO studies using genetic models as noted in [Table 1], it is of interest to assess the phenotypes following a triple KO of all three members of the plastin protein family in the rodent testis since it is likely that other members of the plastin family could supersede the lost function of a plastin family member. Furthermore, it is known that activation of plastins that unleashes its intrinsic bundling activity requires its phosphorylation. For instance, plastin 2 has two phosphorylation sites near its N-terminus, including Ser-5 (primary phosphorylation site) and Ser-7, and it was shown that phosphorylation of plastin 2 at Ser-5 promoted its targeting to an actin microfilament and to enhance its intrinsic bundling activity,  as well as T cell activation. , An impairment of plastin 2 phosphorylation at Ser-5 was recently shown to perturb T cell activation through a disruption of the contact zone between T cells and antigen-presenting cells (APCs) known as the immune synapse.  In studies using HEK294T cells (a human embryonic kidney cell line), PKA, but not PKC, was shown to be the kinase that phosphorylated and activated plastin 2.  Thus, it is of interest and important to determine if PKA (or another protein kinase(s), such as cSrc, cYes, or FAK which are components of the ES ,, ) at the ES is responsible for plastin activation in the testis. There are also other outstanding questions remain. Are different protein kinases involved in plastin activation at different stages of the epithelial cycle via their spatiotemporal expression during the epithelial cycle? Are different kinases being used to activate plastin 1, 2 versus 3 in the testis? The answers to these questions may provide important insightful information on the involvement of plastins and also other actin bundling proteins in spermatogenesis, in particular, the signaling pathway(s) that activate plastins along the seminiferous epithelium during the epithelial cycle.
| Author Contributions|| |
NL and CYC researched on the topic and wrote the first draft; NL and CYC prepared all figures; NL, CKCW and CYC critically evaluated published findings discussed in the paper; CYC prepared the final version; NL, CKCW and CYC read and approved the final version.
| Competing Financial Interests|| |
All authors declare no competing interests.
| Acknowledgments|| |
We thank Dr. Dolores Mruk for the critical discussion during the preparation of this manuscript. This work was supported by grants from the National Institutes of Health (NICHD, R01 HD056034 to CYC and U54 HD029990, Project 5 to CYC).
| References|| |
Morley SC. The actin-bundling protein L-plastin supports T-cell motility and activation. Immunol Rev
2013; 256: 48-62.
Samstag Y. Actin cytoskeletal dynamics in T lymphocyte activation and migration. J Leukoc Biol
2003; 73: 30-48.
Delanote V, Vandekerckhove J, Gettemans J. Plastins: versatile modulators of actin organization in (patho)physiological cellular processes. Acta Pharmacol Sin
2005; 26: 769-79.
dos Remedios CG, Chhabra D, Kekic M, Dedova IV, Tsubakihara M, et al.
Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol Rev
2003; 83: 433-73.
Bartles J. Parallel actin bundles and their multiple actin-bundling proteins. Curr Opin Cell Biol
2000; 12: 72-8.
Yan HH, Mruk DD, Lee WM, Cheng CY. Ectoplasmic specialization: a friend or a foe of spermatogenesis? BioEssays
2007; 29: 36-48.
Wong EW, Mruk DD, Cheng CY. Biology and regulation of ectoplasmic specialization, an atypical adherens junction type, in the testis. Biochem Biophys Acta
2008; 1778: 692-708.
Mruk DD, Cheng CY. Cell-cell interactions at the ectoplasmic specialization in the testis. Trends Endocrinol Metab
2004; 15: 439-47.
Puius YA, Mahoney NM, Almo SC. The modular structure of actin-regulatory proteins. Curr Opin Cell Biol
1998; 10: 23-34.
Matsudaira PT, Burgess DR. Identification and orgganization of the components in the isolated microvillus cytoskeleton. J Cell Biol
1997; 83: 667-73.
Lin CS, Shen WY, Chen ZP, Tu YH, Matsudaira PT. Identification of I-plastin, a humann fimbrin isoform expressed in intestine and kidney. Mol Cell Biol
1994; 14: 2457-67.
Bretscher A, Weber K. Fimbrin, a new microfilament-associated protein present in microvilli and other cell-surface structures. J Cell Biol
1980; 86: 335-40.
Bretscher A. Fimbrin is a cytoskeletal protein that cross-links F-actin in vitro
. Proc Natl Acad Sci U S A
1981; 78: 6849-53.
Glenney JR, Kaulfus P, Matsudaira PT, Weber K. F-actin binding and bundling properties of fimbrin, a major cytoskeletal protein of microvillus core filaments. J Biol Chem
1981; 256: 9283-8.
Goldstein D, Djeu J, Latter G, Burbeck S, Leavitt J. Abundant synthesis of the transformation induced protein of neoplastic human fibroblasts, plastin, in normal lympocytes. Cancer Res
1985; 45: 5643-7.
Lin CS, Aebersold RH, Kent SB, Varma MV, Leavitt J. Molecular cloning and characterziation of plastin, a human leukocyte protein expressed in transformed human fibroblasts. Mol Cell Biol
1998; 8: 4659-68.
Leavitt J, Kakunaga T. Expression of a variant form of actin and additional polypeptide changes following chemical induced in vitro
neoplastic transformation of human fibroblasts. J Biol Chem
1980; 255: 1650-61.
Leavitt J, Goldman D, Merriol C, Kakunaga T. Changes in gene expression accompanying chemically induced malignant transformation of human fibroblasts. Carcinogenesis
1982; 3: 61-70.
Chen H, Mocsai A, Zhang H, Ding RX, Morisaki JH, et al.
Role for plastin in host defense distinguishes integrin signaling from cell adhesion and spreading. Immunity
2003; 19: 95-104.
Tilney MS, Tilney LG, Stephens RE, Merte C, Drenckhahn D, et al.
Preliminary biochemical characterization of the stereocilia and cuticular plate of hari cells of the chick cochlea. J Cell Biol
1989; 109: 1711-23.
Daudet N, Lebart MC. Transient expression of the T-isoform of plastins/fimbrin in the stereocilia of developing autitory hair cells. Cell Motil Cytoskeleton
2002; 53: 326-36.
Shinomiya H. Plastin family of actin-bundling proteins: its functions in leukocytes, neurons, intestines, and cancer. Int J Cell Biol
2012; 2012: 213492.
Oprea GE, Krober S, McWhorter ML, Rossoll W, Muller S, et al.
Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy. Science
2008; 320: 524-7.
van Dijk FS, Zillikens MC, Micha D, Riessland M, Marcelis CL, et al.
PLS3 mutations in X-linked osteoporosis with fractures. N Engl J Med
2013; 369: 1529-36.
Weinbaum S, Duan Y, Thi MM, You L. An integrative review of mechanotransduction in endothelial, epithelial (renal) and dendritic cells (osteocytes). Cell Mol Bioeng
2011; 4: 510-37.
Mulvihill BM, Prendergast PJ. Mechanobiological regulation of the remodelling cycle in trabecular bone and possible biomechanical pathways for osteoporosis. Clin Biomech
2010; 25: 491-8.
Li N, Mruk DD, Wong CK, Lee WM, Han D, et al
. Actin-bundling protein plastin 3 is a regulator of ectoplasmic specialization dynamics during spermatogenesis in the rat testis. FASEB J
2015; 29: 3788-805.
Grimm-Gunter EM, Revenu C, Ramos S, Hurbain I, Smyth N, et al.
Plastin 1 binds to keratin and is required for terminal web assembly in the intestinal epithelium. Mol Biol Cell
2009; 20: 2549-62.
Russell LD. Observations on rat Sertoli ectoplasmic ('junctional') specializations in their association with germ cells of the rat testis. Tissue Cell
1977; 9: 475-98.
Russell LD. Movement of spermatocytes from the basal to the adluminal compartment of the rat testis. Am J Anat
1977; 148: 313-28.
Wong EW, Cheng CY. Polarity proteins and cell-cell interactions in the testis. Int Rev Cell Mol Biol
2009; 278: 309-53.
Vogl AW, Vaid KS, Guttman JA. The Sertoli cell cytoskeleton. Adv Exp Med Biol
2008; 636: 186-211.
Vogl AW, Young JS, Du M. New insights into roles of tubulobulbar complexes in sperm release and turnover of blood-testis barrier. Int Rev Cell Mol Biol
2013; 303: 319-55.
Grove BD, Vogl AW. Sertoli cell ectoplasmic specializations: a type of actin-associated adhesion junction? J Cell Sci
1989; 93: 309-23.
Ozaki-Kuroda K, Nakanishi H, Ohta H, Tanaka H, Kurihara H, et al.
Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions. Curr Biol
2002; 12: 1145-50.
Gungor-Ordueri NE, Tang EI, Celik-Ozenci C, Cheng CY. Ezrin is an actin binding protein that regulates Sertoli cell and spermatid adhesion during spermatogenesis. Endocrinology
2014; 155: 3981-95.
Qian X, Mruk DD, Wong EW, Lie PP, Cheng CY. Palladin is a regulator of actin filament bundles at the ectoplasmic specialization in the rat testis. Endocrinology
2013; 154: 1907-20.
Lie PP, Mruk DD, Lee WM, Cheng CY. Epidermal growth factor receptor pathway substrate 8 (Eps8) is a novel regulator of cell adhesion and the blood-testis barrier integrity in the seminiferous epithelium. FASEB J
2009; 23: 2555-67.
Clermont Y, Morales C, Hermo L. Endocytic activities of Sertoli cells in the rat. Ann N Y Acad Sci
1987; 513: 1-15.
Karpova TS, Tatchell K, Cooper JA. Actin filaments in yeast are unstable in the absence of capping protein or fimbrin. J Cell Biol
1995; 131: 1483-93.
Goodman A, Goode BL, Matsudaira PT, Fink GR. The Saccharomyces cerevisiae
carlponin/transgelin homolog Scp1 functions with fimbrin to regulate stability and organization of the actin cytoskeleton. Mol Biol Cell
2003; 14: 2617-29.
Ghosh M, Song X, Mouneimne G, Sidani M, Lawrence DS, et al.
Cofilin promotes actin polymerization and defines the direction of cell motility. Science
2004; 304: 743-6.
Giganti A, Plastino J, Janji B, Van Troys M, Lentz D, et al.
Actin-filament cross-linking protein T-plastin increases Arp2/3-mediated actin-based movement. J Cell Sci
2005; 118: 1255-65.
Janji B, Giganti A, De Corte V, Catillon M, Bruyneel E, et al.
Phosphorylation on Ser5 increases the F-actin-binding activity of L-plastin and promotes its targeting to sites of actin assembly in cells. J Cell Sci
2006; 119: 1947-60.
Grimbert P, Valanciute A, Audard V, Pawlak A, Legouvelo S, et al.
Truncation of C-mip (Tc-mip), a new proximal signaling protein, induces c-maf Th2 transcription factor and cytoskeleton reorganization. J Exp Med
2003; 198: 797-807.
Sester U, Wabnitz GH, Kirchgessner H, Samstag Y. Ras/PI3kinase/cofilin-independent activation of human CD45RA+ and CD45RO+ T cells by superagonistic CD28 stimulation. Eur J Immunol
2007; 37: 2881-91.
De Clercq S, Zwaenepoel O, Martens E, Vandekerckhove J, Guillabert A, et al.
Nanobody-induced perturbation of LFA-1/L-plastin phosphorylation imparis MTOC docking, immune synpase formation and T cell activation. Cell Mol Life Sci
2013; 70: 909-22.
Xiao X, Mruk DD, Cheng FL, Cheng CY. c-Src and c-Yes are two unlikely partners of spermatogenesis and their roles in blood-testis barrier dynamics. Adv Exp Med Biol
2012; 763: 295-317.
Cheng CY, Mruk DD. Regulation of blood-testis barrier dynamics by focal adhesion kinase (FAK). An unexpected turn of events. Cell Cycle
2009; 8: 3493-9.
Li SY, Mruk DD, Cheng CY. Focal adhesion kinase is a regulator of F-actin dynamics: new insights from studies in the testis. Spermatogenesis
2013; 3: e25385.
Lin CS, Park T, Chen ZP, Leavitt J. Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells. J Biol Chem
1993; 268: 2781-92.
Taylor R, Bullen A, Johnson SL, Grimm-Gunter EM, Rivero F, et al.
Absence of plastin 1 causes abnormal maintenance of hair cell stereocilia and a moderate form of hearing loss in mice. Hum Mol Genet
2015; 24: 37-49.
Namba Y, Ito M, Zu Y, Shigesada K, Maruyama K. Human T cell L-plastin bundles actin filaments in a calcium-dependent manner. J Biochem
1992; 112: 503-7.
Correia I, Chu D, Chou YH, Goldman RD, Matsudaira P. Integrating the actin and vimentin cytoskeletons. adhesion-dependent formation of fimbrin-vimentin complexes in macrophages. J Cell Biol
1999; 146: 831-42.
Ohsawa K, Imai Y, Sasaki Y, Kohsaka S. Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity. J Neurochem
2004; 88: 844-56.
Hagiwara M, Shinomiya H, Kashihara M, Kobayashi K, Tadokoro T, et al.
Interaction of activated Rab5 with actin-bundling proteins, L- and T-plastin and its relevance to endocytic functions in mammalian cells. Biochem Biophys Res Commun
2011; 407: 615-9.
Kondo I, Shin K, Honmura S, Nakajima H, Yamamura E, et al
. A case report of a patient with retinoblastoma and chromosome 13q deletion: assignment of a new gene (gene for LCP1) on human chromosome 13. Hum Genet
1985; 71: 263-6.
Todd EM, Deady LE, Morley SC. The actin-bundling protein L-plastin is essential for marginal zone B cell development. J Immunol
2011; 187: 3015-25.
Wang C, Morley SC, Donermeyer D, Peng I, Lee WP, et al.
Actin-bundling protein L-plastin regulates T cell activation. J Immunol
2010; 185: 7487-97.
Todd EM, Deady LE, Morley SC. Intrinsic T- and B-cell defects impair T-cell-dependent antibody responses in mice lacking the actin-bundling protein L-plastin. Eur J Immunol
2013; 43: 1735-44.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
|This article has been cited by|
||Plastin 3 in X-Linked Osteoporosis: Imbalance of Ca2+-Dependent Regulation Is Equivalent to Protein Loss
| ||Christopher L. Schwebach,Elena Kudryashova,Dmitri S. Kudryashov |
| ||Frontiers in Cell and Developmental Biology. 2021; 8 |
|[Pubmed] | [DOI]|
||The proteomic characterization of ram sperm during cryopreservation analyzed by the two-dimensional electrophoresis coupled with mass spectrometry
| ||Chunrong Lv,Allai Larbi,Sameeullah Memon,Jiachong Liang,Xueming Zhao,Qingyong Shao,Guoquan Wu,Guobo Quan |
| ||Cryobiology. 2020; |
|[Pubmed] | [DOI]|
||The dynamics and regulation of microfilament during spermatogenesis
| ||Tong Yang,Wan-Xi Yang |
| ||Gene. 2020; 744: 144635 |
|[Pubmed] | [DOI]|
||Peptidomimetic inhibitors of L-plastin reduce the resorptive activity of osteoclast but not the bone forming activity of osteoblasts in vitro
| ||Meenakshi A. Chellaiah,Sunipa Majumdar,Hanan Aljohani,Sakamuri V. Reddy |
| ||PLOS ONE. 2018; 13(9): e0204209 |
|[Pubmed] | [DOI]|
||Rabbit seminal plasma proteome: The importance of the genetic origin
| ||Lucía Casares-Crespo,Paula Fernández-Serrano,José S. Vicente,Francisco Marco-Jiménez,María Pilar Viudes-de-Castro |
| ||Animal Reproduction Science. 2017; |
|[Pubmed] | [DOI]|