NC1 domain of collagen α3(IV) derived from the basement membrane regulates Sertoli cell blood-testis barrier dynamics

Wong, Elissa W.P.; Cheng, C. Yan

doi:10.4161/spmg.25465

Cited by 34 publications

(41 citation statements)

References 77 publications

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“…Rat collagen α3(IV) chain NC1 domain was cloned as previously described (34), which also served as the template to clone pCI‐neo/NC1 that contained the putative signal peptide (SP) of rat collagen α3(IV) chain, namely pCI‐neo/rat SP (rSP)‐NC1. Four sequential overlapping PCRs were performed to add the putative SP (Supplemental Fig.…”

Section: Methodsmentioning

confidence: 99%

Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane–derived noncollagenous 1 domain peptide

et al. 2017

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Spermatogenesis takes place in the epithelium of the seminiferous tubules of the testes, producing millions of spermatozoa per day in an adult male in rodents and humans. Thus, multiple cellular events that are regulated by an array of signaling molecules and pathways are tightly coordinated to support spermatogenesis. Here, we report findings of a local regulatory axis between the basement membrane (BM), the blood-testis barrier (BTB), and the apical ectoplasmic specialization (apical ES; a testis-specific, actin-rich adherens junction at the Sertoli cell-spermatid interface) to coordinate cellular events across the seminiferous epithelium during the epithelial cycle. In short, a biologically active fragment, noncollagenous 1 (NC1) domain that is derived from collagen chains in the BM, was found to modulate cell junction dynamics at the BTB and apical ES. NC1 domain from the collagen a3(IV) chain was cloned into a mammalian expression vector, pCI-neo, with and without a collagen signal peptide. We also prepared a specific Ab against the purified recombinant NC1 domain peptide. These reagents were used to examine whether overexpression of NC1 domain with high transfection efficacy would perturb spermatogenesis, in particular, spermatid adhesion (i.e., inducing apical ES degeneration) and BTB function (i.e., basal ES and tight junction disruption, making the barrier leaky), in the testis in vivo. We report our findings that NC1 domain derived from collagen a3(IV) chain-a major structural component of the BM-was capable of inducing BTB remodeling, making the BTB leaky in studies in vivo. Furthermore, NC1 domain peptide was transported across the epithelium via a microtubule-dependent mechanism and is capable of inducing apical ES degeneration, which leads to germ cell exfoliation from the seminiferous epithelium. Of more importance, we show that NC1 domain peptide exerted its regulatory effect by disorganizing actin microfilaments and microtubules in Sertoli cells so that they failed to support cell adhesion and transport of germ cells and organelles (e.g., residual bodies, phagosomes) across the seminiferous epithelium. This local regulatory axis between the BM, BTB, and the apical ES thus coordinates cellular events that take place across the seminiferous epithelium during the epithelial cycle of spermatogenesis.-Chen, H., Mruk, D. D., Lee, W. M., Cheng, C. Y. Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane-derived noncollagenous 1 domain peptide. FASEB J. 31, 3587-3607 (2017). www.fasebj.orgIn the mammalian testis, basement membrane (BM), a modified form of the extracellular matrix and a product of Sertoli and peritubular myoid cells (1, 2), is mostly constituted by type IV collagen, laminins (e.g., laminin a1, a2, b1, b2, g1), heparin sulfate proteoglycan, and nidogen (formerly called entactin) (3-5). As BM is in direct contact with Sertoli cells in the seminiferous epithelium, it is likely that there are crosstalks between Sertoli cells and the B...

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Section: Methodsmentioning

confidence: 99%

Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane–derived noncollagenous 1 domain peptide

et al. 2017

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“…For instance, what molecule(s) and/or signaling pathway(s) are involved in coordinating both the events of spermiation and BTB restructuring which take place simultaneously at stage VIII but across the seminiferous epithelium? It is likely that biologically active fragments of laminin chains that are formed during apical ES degeneration at late stage VIII are involved in coordinating these events [51, 52], however, the biology of collagen fragments (e.g., non-collagenous domain 1, NC1) generated at the basement membrane that modulates BTB dynamics [110, 111] remains to be better elucidated. Also, does cytokine(s) (e.g., TGF-β3, TNFα) play any roles in these events since studies have shown that cytokines released by Sertoli and/or germ cells into the microenvironment of the ES regulate cell adhesion [112-114]?…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Role of non-receptor protein tyrosine kinases in spermatid transport during spermatogenesis

Wan¹,

Mruk²,

Tang³

et al. 2014

Seminars in Cell & Developmental Biology

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Non-receptor protein tyrosine kinases are cytoplasmic kinases that activate proteins by phosphorylating target protein tyrosine residues, in turn affecting multiple functions in eukaryotic cells. Herein, we focus on the role of non-receptor protein tyrosine kinases, most notably, FAK, c-Yes and c-Src, in the transport of spermatids across the seminiferous epithelium during spermatogenesis. Since spermatids, which are formed from spermatocytes via meiosis, are immotile haploid cells, they must be transported by Sertoli cells across the seminiferous epithelium during the epithelial cycle of spermatogenesis. Without the timely transport of spermatids across the epithelium, the release of sperms at spermiation fails to occur, leading to infertility. Thus, the molecular event pertinent to spermatid transport is crucial to spermatogenesis. Herein, we provide a critical discussion based on recent findings in the field. We also provide a hypothetical model on spermatid transport, and the role of non-receptor protein tyrosine kinases in this event. We also highlight areas of research that deserve attention by investigators in the field.

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“…On the other hand, recent studies have shown that BTB dynamics in the rat testis are supported and regulated by local functional axis involving biologically active fragments released from the apical ES (at the Sertoli-spermatid interface in the adluminal compartment from step 8–19 spermatids) such as the F5 peptide from the laminin chains [30–32], and also peptides from the collagen α3 (IV) chain (e.g., non-collagenous 1, NC1, domain peptide) [33] and laminin α2 chain (e.g., 80 kDa fragment) [34, 35]. These findings are also supported by studies using toxicant-induced Sertoli cell injury animal models, such as the use of phthalates [36, 37].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

Wen

Tang

et al. 2018

Methods in Molecular Biology

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The blood-testis barrier (BTB) is an important ultrastructure in the testis that supports meiosis and postmeiotic spermatid development since a delay in the establishment of a functional Sertoli cell barrier during postnatal development in rats or mice by 17–20 day postpartum (dpp) would lead to a delay of the first wave of meiosis. Furthermore, irreversible disruption of the BTB by toxicants also induces infertility in rodents. Herein, we summarize recent findings that BTB dynamics (i.e., disassembly, reassembly, and stabilization) are supported by the concerted efforts of the actin- and microtubule (MT)-based cytoskeletons. We focus on the role of two actin nucleation protein complexes, namely, the Arp2/3 (actin-related protein 2/3) complex and formin 1 (or the formin 1/spire 1 complex) known to induce actin nucleation, respectively, by conferring plasticity to actin cytoskeleton. We also focus on the MT plus (+)-end tracking protein (+TIP) EB1 (end-binding protein 1) which is known to confer MT stabilization. Furthermore, we discuss in particular how the interactions of these proteins modulate BTB dynamics during spermatogenesis. These findings also yield a novel hypothetical concept regarding the molecular mechanism that modulates BTB function.

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NC1 domain of collagen α3(IV) derived from the basement membrane regulates Sertoli cell blood-testis barrier dynamics

Cited by 34 publications

References 77 publications

Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane–derived noncollagenous 1 domain peptide

Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane–derived noncollagenous 1 domain peptide

Role of non-receptor protein tyrosine kinases in spermatid transport during spermatogenesis

Regulation of Blood-Testis Barrier (BTB) Dynamics, Role of Actin-, and Microtubule-Based Cytoskeletons

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