Ⅳ型胶原蛋白NC1片段在精子发生及血睾屏障中作用的研究进展

doi:10.16352/j.issn.1001-6325.2023.04.0532

摘要/Abstract

摘要： 在哺乳动物睾丸中,位于生精上皮基底膜附近的血睾屏障(blood-testis barrier,BTB)对精子发生至关重要。BTB由相邻的支持细胞(Sertoli细胞)连接而成,将生精上皮分为靠近基底膜的“基底室”和靠近生精小管管腔的“近腔室”,为精子发生提供了免疫屏障。Ⅳ型胶原蛋白是基底膜的重要组成成分,啮齿类动物的睾丸中Ⅳ型胶原蛋白主要是由3条α3链组成的三螺旋结构。大鼠睾丸的Ⅳ型胶原蛋白α3链C端可以水解成大小为28 ku的蛋白片段,称为C端非胶原结构域(noncollagenous domain -peptide,NC1片段)。NC1片段作为一种基底膜源性多肽在参与精子发生与维系BTB功能方面发挥了重要作用。本文通过分析、总结近期研究结果,概述Ⅳ型胶原蛋白NC1片段在睾丸中的作用及其机制,尤其是其在精子发生与BTB中作用的研究进展。

关键词: 精子发生, 血睾屏障(BTB), Ⅳ型胶原蛋白, NC1片段

Abstract: In mammalian testis, the blood-testis barrier (BTB), located near the basement membrane of seminiferous epithelium, is essential for spermatogenesis. BTB is formed by the joining of adjacent Sertoli cells and divides the seminiferous epithelium into basal compartment near the basement membrane and apical compartment near the lumen of spermatogenic tubules. The barrier provides an immune defense mechanism for spermatogenesis. Type Ⅳ collagen is an important component of basement membrane. In rodent testis, type Ⅳ collagen is mainly composed of three α3 chains in a triple helix structure. The C-terminal noncollagenous domain (NC1 domain) of type Ⅳ collagen α3 chain of rat testis can be hydrolyzed into a 28 ku protein fragment called NC1 domain. NC1 domain as a basement membrane peptide is involved in spermatogenesis and sustains BTB function. This article reviews recent research results in order to identify the role of type Ⅳ collagen NC1 domain in testis and underlying mechanisms, mainly focuses on spermatogenesis and BTB.

Key words: spermatogenesis, blood-testis barrier (BTB), type Ⅳ collagen, C-terminal noncollagenous domain (NC1 domain)

中图分类号:

蒋术一, 宿文辉. Ⅳ型胶原蛋白NC1片段在精子发生及血睾屏障中作用的研究进展[J]. 基础医学与临床, 2023, 43(4): 532-537.

JIANG Shuyi, SU Wenhui. Advances in the effect of NC1 domain of type Ⅳ collagen on spermatogenesis and blood-testis barrier[J]. Basic & Clinical Medicine, 2023, 43(4): 532-537.

参考文献

[1]Tajaddini S, Ebrahimi S, Behnam B, et al. Antioxidant effect of manganese on the testis structure and sperm parameters of formalin-treated mice[J]. Andrologia, 2014, 46: 246-253.
[2]Wong EW, Cheng CY. Polarity proteins and cell-cell interactions in the testis[J]. Int Rev Cell Mol Biol, 2009, 278: 309-353.
[3]Setchell BP. Blood-testis barrier, junctional and transport proteins and spermatogenesis[J]. Adv Exp Med Biol, 2008, 636: 212-233.
[4]Gao Y, Mruk DD, Lui WY, et al. F5-peptide induces aspermatogenesis by disrupting organization of actin- and microtubule-based cytoskeletons in the testis[J]. Oncotarget, 2016, 7: 64203-64220.
[5]Li H, Liu S, Wu S, et al. Bioactive fragments of laminin and collagen chains: lesson from the testis[J]. Reproduction, 2020, 159: R111-R123.
[6]Skinner MK, Tung PS, Fritz IB. Cooperativity between Sertoli cells and testicular peritubular cells in the production and deposition of extracellular matrix components[J]. J Cell Biol, 1985, 100: 1941-1947.
[7]Skinner MK, Fritz IB. Structural characterization of proteoglycans produced by testicular peritubular cells and Sertoli cells[J]. J Biol Chem, 1985, 260: 11874-11883.
[8]Murdock MH, David S, Swinehart IT, et al. Human testis extracellular matrix enhances human spermatogonial stem cell survival in vitro[J]. Tissue Eng Part A, 2019, 25: 663-676.
[9]Hager M, Gawlik K, Nystrom A, et al. Laminin {alpha}1 chain corrects male infertility caused by absence of laminin {alpha}2 chain[J]. Am J Pathol, 2005, 167: 823-833.
[10]Sorushanova A, Delgado LM, Wu Z, et al. The collagen suprafamily: from biosynthesis to advanced biomaterial development[J]. Adv Mater, 2019, 31: e1801651.
[11]Nagy N, Barad C, Hotta R, et al. Collagen 18 and agrin are secreted by neural crest cells to remodel their microenvironment and regulate their migration during enteric nervous system development[J]. Development, 2018, 145: dev160317.
[12]Haronen H, Zainul Z, Tu H, et al. Collagen XIII secures pre- and postsynaptic integrity of the neuromuscular synapse[J]. Hum Mol Genet, 2017, 26: 2076-2090.
[13]Ricard-Blum S. The collagen family[J]. Cold Spring Harb Perspect Biol, 2011, 3: a004978.doi:10.1101/cshperspect.a004978.
[14]Rebustini IT, Myers C, Lassiter KS, et al. MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis[J]. Dev Cell, 2009, 17: 482-493.
[15]Wang Z, Zhai Z, Chen C, et al. Air pollution particles hijack peroxidasin to disrupt immunosurveillance and promote lung cancer[J]. Elife, 2022, 11: e75345.
[16]LeBleu V, Sund M, Sugimoto H, et al. Identification of the NC1 domain of {alpha}3 chain as critical for {alpha}3{alpha}4{alpha}5 type IV collagen network assembly[J]. J Biol Chem, 2010, 285: 41874-41885.
[17]Hamano Y, Kalluri R. Tumstatin, the NC1 domain of alpha3 chain of type IV collagen, is an endogenous inhibitor of pathological angiogenesis and suppresses tumor growth[J]. Biochem Biophys Res Commun, 2005, 333: 292-298.
[18]Wong EW, Cheng CY. NC1 domain of collagen alpha3(IV) derived from the basement membrane regulates Sertoli cell blood-testis barrier dynamics[J]. Spermatogenesis, 2013, 3: e25465.
[19]Jiang S, Xu Y, Fan Y, et al. Busulfan impairs blood-testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9[J]. Andrology, 2022, 10: 377-391.
[20]Chen H, Mruk DD, Lee WM, et al. Regulation of spermatogenesis by a local functional axis in the testis: role of the basement membrane-derived noncollagenous 1 domain peptide[J]. FASEB J, 2017, 31: 3587-3607.
[21]Vogl AW, Vaid KS, Guttman JA. The Sertoli cell cytoskeleton[J]. Adv Exp Med Biol, 2008, 636: 186-211.
[22]Wong EW, Mruk DD, Cheng CY. Biology and regulation of ectoplasmic specialization, an atypical adherens junction type, in the testis[J]. Biochim Biophys Acta, 2008, 1778: 692-708.
[23]Li MW, Mruk DD, Cheng CY. Gap junctions and blood-tissue barriers[J]. Adv Exp Med Biol, 2012, 763: 260-280.
[24]O'Donnell L, O'Bryan MK. Microtubules and spermatogenesis[J]. Semin Cell Dev Biol, 2014, 30: 45-54.
[25]O'Donnell L. Mechanisms of spermiogenesis and spermia-tion and how they are disturbed[J]. Spermatogenesis, 2014, 4: e979623.
[26]Tang EI, Mruk DD, Cheng CY. Regulation of microtubule (MT)-based cytoskeleton in the seminiferous epithelium during spermatogenesis[J]. Semin Cell Dev Biol, 2016, 59: 35-45.
[27]Bonello TT, Peifer M. Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation[J]. J Cell Biol, 2019, 218: 742-756.
[28]Wen Q, Mruk D, Tang EI, et al. Cell polarity and cytoskeletons-lesson from the testis[J]. Semin Cell Dev Biol, 2018, 81: 21-32.
[29]Li L, Gao Y, Chen H, et al. Cell polarity, cell adhesion, and spermatogenesis: role of cytoskeletons[J]. F1000Res, 2017, 6: 1565.
[30]Chen H, Mruk DD, Lee WM, et al. Planar cell polarity (PCP) protein Vangl2 regulates ectoplasmic specializa-tion dynamics via its effects on actin microfilaments in the testes of male rats[J]. Endocrinology, 2016, 157: 2140-2159.
[31]Chen H, Xiao X, Lui WY, et al. Vangl2 regulates spermatid planar cell polarity through microtubule (MT)-based cytoskeleton in the rat testis[J]. Cell Death Dis, 2018, 9: 340.
[32]Li L, Mao B, Yan M, et al. Planar cell polarity protein Dishevelled 3 (Dvl3) regulates ectoplasmic specialization (ES) dynamics in the testis through changes in cytoskeletal organization[J]. Cell Death Dis, 2019, 10: 194.
[33]Chen H, Mruk DD, Lui WY, et al. Cell polarity and planar cell polarity (PCP) in spermatogenesis[J]. Semin Cell Dev Biol, 2018, 81: 71-77.
[34]Li L, Mao B, Wu S, et al. Regulation of spermatid polarity by the actin- and microtubule (MT)-based cytoskeletons[J]. Semin Cell Dev Biol, 2018, 81: 88-96.
[35]Liu S, Li H, Wu S, et al. NC1-peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1[J]. FASEB J, 2020, 34: 3105-3128.
[36]Magaway C, Kim E, Jacinto E. Targeting mTOR and metabolism in cancer: lessons and innovations[J]. Cells, 2019, 8: 1584.
[37]Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast[J]. Science, 1991, 253: 905-909.
[38]Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast[J]. J Biol Chem, 1998, 273: 3963-3966.
[39]Li N, Cheng CY. Mammalian target of rapamycin complex (mTOR) pathway modulates blood-testis barrier (BTB) function through F-actin organization and gap junction[J]. Histol Histopathol, 2016, 31: 961-968.
[40]Mok KW, Chen H, Lee WM, et al. rpS6 regulates blood-testis barrier dynamics through Arp3-mediated actin microfilament organization in rat sertoli cells. An in vitro study[J]. Endocrinology, 2015, 156: 1900-1913.
[41]Mok KW, Mruk DD, Cheng CY. rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9[J]. J Cell Sci, 2014, 127: 4870-4882.
[42]Mok KW, Mruk DD, Silvestrini B, et al. rpS6 Regulates blood-testis barrier dynamics by affecting F-actin organization and protein recruitment[J]. Endocrinology, 2012, 153: 5036-5048.
[43]Su W, Cheng CY. Cdc42 is involved in NC1 peptide-regulated BTB dynamics through actin and microtubule cytoskeletal reorganization[J]. FASEB J, 2019, 33: 14461-14478.
[44]Etienne-Manneville S, Hall A. Rho GTPases in cell biology[J]. Nature, 2002, 420: 629-635.
[45]Ma L, Rohatgi R, Kirschner MW. The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42[J]. Proc Natl Acad Sci U S A, 1998, 95: 15362-15367.
[46]Rohatgi R, Ho HY, Kirschner MW. Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4, 5-bisphosphate[J]. J Cell Biol, 2000, 150: 1299-1310.