精子领形成及精子领内运输相关蛋白的研究进展

doi:10.12280/gjszjk.20210535

摘要/Abstract

摘要：

精子领（manchette）是一种暂时存在于精子形成过程中的结构,主要由微管和肌动蛋白构成。作为细胞骨架的特殊组织形式,精子领还与精子细胞中的核骨架及中心体存在相互作用。在精子细胞变形过程中,精子领是运输囊泡和蛋白质的重要平台,其结构或功能异常可能导致鞭毛组装及精子核成形障碍,最终影响雄性生育能力。综述精子领的结构组成、形成及解聚、精子领内运输（intra-manchette transport,IMT）及调控机制。其中,调控精子领形成及维持的蛋白包括钩蛋白家族、中心体蛋白家族、纤毛及鞭毛相关蛋白家族等;参与IMT的蛋白包括驱动蛋白家族、鞭毛内运输蛋白复合体-B等。深入了解精子领相关机制有助于阐明部分男性生精障碍病例的病因及病理机制,也可为男性避孕方法的开发提供新的思路。

关键词: 精子发生, 细胞骨架, 精子领, 精子领内运输, 生精障碍

Abstract:

Manchette is the structure that transiently exists in the process of spermiogenesis, mainly composed of microtubules and actins. As a specialized part of cytoskeleton in spermatids, manchette also interacts with the nuclear skeleton and centrosome. Manchette is actually a platform for the vesicles and proteins transportation during the spermatid transformation. Therefore, the malformation and/or dysfunction of the manchette may lead to the failure of flagella assembly and/or sperm head shaping, ultimately causing negative effects on male fertility. This review introduces the recent research progresses on the manchette dynamics and intra-manchette transport (IMT), especially the related regulators. Among which, the proteins regulating the formation and maintenance of manchette include hook protein family, centrosomal protein family, cilia- and flagella-associated proteins, etc. The factors participating in the IMT include the kinesin family, intraflagellar transport complex-B and so on. The more understanding of the manchette will help us to clarify the etiology and pathology of male spermatogenic disorders, and also provide us new idea for the development of male contraceptive methods.

Key words: Spermatogenesis, Cytoskeleton, Manchette, Intra-manchette transport, Dyszoospermia

王心依, 王治琪, 王珺, 徐琴舟, 夏小雨. 精子领形成及精子领内运输相关蛋白的研究进展[J]. 国际生殖健康/计划生育, 2022, 41(2): 129-134.

WANG Xin-yi, WANG Zhi-qi, WANG Jun, XU Qin-zhou, XIA Xiao-yu. Regulation of Manchette Formation and Intra-Manchette Transport[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(2): 129-134.

参考文献 47

[1]	Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis[M]. Berlin:Grosse, 1981.
[2]	Chen SR, Batool A, Wang YQ, et al. The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon′s head to tail[J]. Cell Death Dis, 2016, 7(11):e2472. doi: 10.1038/cddis.2016.344. doi: 10.1038/cddis.2016.344 URL
[3]	Lehti MS, Sironen A. Formation and function of the manchette and flagellum during spermatogenesis[J]. Reproduction, 2016, 151(4):R43-R54. doi: 10.1530/REP-15-0310. doi: 10.1530/REP-15-0310 URL
[4]	Mochida K, Rivkin E, Gil M, et al. Keratin 9 is a component of the perinuclear ring of the manchette of rat spermatids[J]. Dev Biol, 2000, 227(2):510-519. doi: 10.1006/dbio.2000.9911. doi: 10.1006/dbio.2000.9911 pmid: 11071770
[5]	Kato A, Nagata Y, Todokoro K. Delta-tubulin is a component of intercellular bridges and both the early and mature perinuclear rings during spermatogenesis[J]. Dev Biol, 2004, 269(1):196-205. doi: 10.1016/j.ydbio.2004.01.026. doi: 10.1016/j.ydbio.2004.01.026 URL
[6]	Gao Q, Khan R, Yu C, et al. The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis[J]. J Biol Chem, 2020, 295(19):6289-6298. doi: 10.1074/jbc.RA119.012375. doi: 10.1074/jbc.RA119.012375 URL
[7]	Mendoza-Lujambio I, Burfeind P, Dixkens C, et al. The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse[J]. Hum Mol Genet, 2002, 11(14):1647-1658. doi: 10.1093/hmg/11.14.1647. doi: 10.1093/hmg/11.14.1647 pmid: 12075009
[8]	Chen H, Zhu Y, Zhu Z, et al. Detection of heterozygous mutation in hook microtubule-tethering protein 1 in three patients with decapitated and decaudated spermatozoa syndrome[J]. J Med Genet, 2018, 55(3):150-157. doi: 10.1136/jmedgenet-2016-104404. doi: 10.1136/jmedgenet-2016-104404 URL
[9]	Zhou J, Du YR, Qin WH, et al. RIM-BP3 is a manchette-associated protein essential for spermiogenesis[J]. Development, 2009, 136(3):373-382. doi: 10.1242/dev.030858. doi: 10.1242/dev.030858 URL
[10]	Liu Y, DeBoer K, de Kretser DM, et al. LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility[J]. PLoS Genet, 2015, 11(3):e1005090. doi: 10.1371/journal.pgen.1005090. doi: 10.1371/journal.pgen.1005090 URL
[11]	Okuda H, DeBoer K, O′Connor AE, et al. LRGUK1 is part of a multiprotein complex required for manchette function and male fertility[J]. FASEB J, 2017, 31(3):1141-1152. doi: 10.1096/fj.201600909R. doi: 10.1096/fj.201600909R URL
[12]	Calvi A, Wong AS, Wright G, et al. SUN4 is essential for nuclear remodeling during mammalian spermiogenesis[J]. Dev Biol, 2015, 407(2):321-330. doi: 10.1016/j.ydbio.2015.09.010. doi: 10.1016/j.ydbio.2015.09.010 URL
[13]	Kazarian E, Son H, Sapao P, et al. SPAG17 Is Required for Male Germ Cell Differentiation and Fertility[J]. Int J Mol Sci, 2018, 19(4):1252. doi: 10.3390/ijms19041252. doi: 10.3390/ijms19041252 URL
[14]	Liu Q, Guo Q, Guo W, et al. Loss of CEP70 function affects acrosome biogenesis and flagella formation during spermiogenesis[J]. Cell Death Dis, 2021, 12(5):478. doi: 10.1038/s41419-021-03755-z. doi: 10.1038/s41419-021-03755-z URL
[15]	Hall EA, Keighren M, Ford MJ, et al. Acute versus chronic loss of mammalian Azi1/Cep131 results in distinct ciliary phenotypes[J]. PLoS Genet, 2013, 9(12):e1003928. doi: 10.1371/journal.pgen.1003928. doi: 10.1371/journal.pgen.1003928 URL
[16]	Tang S, Wang X, Li W, et al. Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella[J]. Am J Hum Genet, 2017, 100(6):854-864. doi: 10.1016/j.ajhg.2017.04.012. doi: 10.1016/j.ajhg.2017.04.012 URL
[17]	Yu Y, Wang J, Zhou L, et al. CFAP43-mediated intra-manchette transport is required for sperm head shaping and flagella formation[J]. Zygote, 2021, 29(1):75-81. doi: 10.1017/S0967199420000556. doi: 10.1017/S0967199420000556 URL
[18]	Wang W, Tian S, Nie H, et al. CFAP65 is required in the acrosome biogenesis and mitochondrial sheath assembly during spermiogenesis[J]. Hum Mol Genet, 2021, 30(23):2240-2254. doi: 10.1093/hmg/ddab185. doi: 10.1093/hmg/ddab185 URL
[19]	Akhmanova A, Mausset-Bonnefont AL, van Cappellen W, et al. The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis[J]. Genes Dev, 2005, 19(20):2501-2515. doi: 10.1101/gad.344505. doi: 10.1101/gad.344505 URL
[20]	Umer N, Arévalo L, Phadke S, et al. Loss of Profilin3 Impairs Spermiogenesis by Affecting Acrosome Biogenesis, Autophagy, Manchette Development and Mitochondrial Organization[J]. Front Cell Dev Biol, 2021, 9:749559. doi: 10.3389/fcell.2021.749559. doi: 10.3389/fcell.2021.749559 URL
[21]	Lin YH, Huang CY, Ke CC, et al. ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects[J]. Biomedicines, 2020, 8(11):518. doi: 10.3390/biomedicines8110518. doi: 10.3390/biomedicines8110518 URL
[22]	Ma Q, Cao C, Zhuang C, et al. AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility[J]. Cell Death Discov, 2021, 7(1):348. doi: 10.1038/s41420-021-00738-z. doi: 10.1038/s41420-021-00738-z URL
[23]	Ma DD, Wang DH, Yang WX. Kinesins in spermatogenesis[J]. Biol Reprod, 2017, 96(2):267-276. doi: 10.1095/biolreprod.116.144113. doi: 10.1095/biolreprod.116.144113 URL
[24]	Olenick MA, Holzbaur E. Dynein activators and adaptors at a glance[J]. J Cell Sci, 2019, 132(6):jcs227132. doi: 10.1242/jcs.227132. doi: 10.1242/jcs.227132
[25]	Teves ME, Roldan E, Krapf D, et al. Sperm Differentiation: The Role of Trafficking of Proteins[J]. Int J Mol Sci, 2020, 21(10):3702. doi: 10.3390/ijms21103702. doi: 10.3390/ijms21103702 URL
[26]	Leslie JS, Rawlins LE, Chioza BA, et al. MNS1 variant associated with situs inversus and male infertility[J]. Eur J Hum Genet, 2020, 28(1):50-55. doi: 10.1038/s41431-019-0489-z. doi: 10.1038/s41431-019-0489-z URL
[27]	Lehti MS, Kotaja N, Sironen A. KIF3A is essential for sperm tail formation and manchette function[J]. Mol Cell Endocrinol, 2013, 377(1/2):44-55. doi: 10.1016/j.mce.2013.06.030. doi: 10.1016/j.mce.2013.06.030 URL
[28]	San Agustin JT, Pazour GJ, Witman GB. Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm[J]. Mol Biol Cell, 2015, 26(24):4358-4372. doi: 10.1091/mbc.E15-08-0578. doi: 10.1091/mbc.E15-08-0578 URL
[29]	Shi L, Zhou T, Huang Q, et al. Intraflagellar transport protein 74 is essential for spermatogenesis and male fertility in mice?[J]. Biol Reprod, 2019, 101(1):188-199. doi: 10.1093/biolre/ioz071. doi: 10.1093/biolre/ioz071 URL
[30]	Zhang Y, Liu H, Li W, et al. Intraflagellar transporter protein (IFT27), an IFT25 binding partner, is essential for male fertility and spermiogenesis in mice[J]. Dev Biol, 2017, 432(1):125-139. doi: 10.1016/j.ydbio.2017.09.023. doi: S0012-1606(17)30463-3 pmid: 28964737
[31]	Liu H, Li W, Zhang Y, et al. IFT25, an intraflagellar transporter protein dispensable for ciliogenesis in somatic cells, is essential for sperm flagella formation[J]. Biol Reprod, 2017, 96(5):993-1006. doi: 10.1093/biolre/iox029. doi: 10.1093/biolre/iox029 URL
[32]	Nozawa YI, Yao E, Gacayan R, et al. Mammalian Fused is essential for sperm head shaping and periaxonemal structure formation during spermatogenesis[J]. Dev Biol, 2014, 388(2):170-180. doi: 10.1016/j.ydbio.2014.02.002. doi: 10.1016/j.ydbio.2014.02.002 pmid: 24525297
[33]	Li W, Huang Q, Zhang L, et al. A single amino acid mutation in the mouse MEIG1 protein disrupts a cargo transport system necessary for sperm formation[J]. J Biol Chem, 2021, 297(5):101312. doi: 10.1016/j.jbc.2021.101312. doi: 10.1016/j.jbc.2021.101312 URL
[34]	Li W, Tang W, Teves ME, et al. A MEIG1/PACRG complex in the manchette is essential for building the sperm flagella[J]. Development, 2015, 142(5):921-930. doi: 10.1242/dev.119834. doi: 10.1242/dev.119834 URL
[35]	Lehti MS, Zhang FP, Kotaja N, et al. SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation[J]. Development, 2017, 144(14):2683-2693. doi: 10.1242/dev.152108. doi: 10.1242/dev.152108 pmid: 28619825
[36]	Zheng C, Ouyang YC, Jiang B, et al. Non-canonical RNA polyadenylation polymerase FAM46C is essential for fastening sperm head and flagellum in mice[J]. Biol Reprod, 2019, 100(6):1673-1685. doi: 10.1093/biolre/ioz083. doi: 10.1093/biolre/ioz083 URL
[37]	O′Donnell L, Rhodes D, Smith SJ, et al. An essential role for katanin p80 and microtubule severing in male gamete production[J]. PLoS Genet, 2012, 8(5):e1002698. doi: 10.1371/journal.pgen.1002698. doi: 10.1371/journal.pgen.1002698 URL
[38]	Ho UY, Feng CA, Yeap YY, et al. WDR62 is required for centriole duplication in spermatogenesis and manchette removal in spermiogenesis[J]. Commun Biol, 2021, 4(1):645. doi: 10.1038/s42003-021-02171-5. doi: 10.1038/s42003-021-02171-5 URL
[39]	Dunleavy J, Okuda H, O′Connor AE, et al. Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse[J]. PLoS Genet, 2017, 13(11):e1007078. doi: 10.1371/journal.pgen.1007078. doi: 10.1371/journal.pgen.1007078 URL
[40]	Bao J, Wu Q, Song R, et al. RANBP17 is localized to the XY body of spermatocytes and interacts with SPEM1 on the manchette of elongating spermatids[J]. Mol Cell Endocrinol, 2011, 333(2):134-142. doi: 10.1016/j.mce.2010.12.021. doi: 10.1016/j.mce.2010.12.021 URL
[41]	Shi Y, Zhang L, Song S, et al. The mouse transcription factor-like 5 gene encodes a protein localized in the manchette and centriole of the elongating spermatid[J]. Andrology, 2013, 1(3):431-439. doi: 10.1111/j.2047-2927.2013.00069.x. doi: 10.1111/j.2047-2927.2013.00069.x pmid: 23444080
[42]	Qi Y, Jiang M, Yuan Y, et al. ADP-ribosylation factor-like 3, a manchette-associated protein, is essential for mouse spermiogenesis[J]. Mol Hum Reprod, 2013, 19(5):327-335. doi: 10.1093/molehr/ gat001. doi: 10.1093/molehr/ gat001 URL
[43]	Schwarz T, Prieler B, Schmid JA, et al. Ccdc181 is a microtubule-binding protein that interacts with Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia[J]. Eur J Cell Biol, 2017, 96(3):276-288. doi: 10.1016/j.ejcb.2017.02.003. doi: S0171-9335(16)30178-9 pmid: 28283191
[44]	Tapia Contreras C, Hoyer-Fender S. CCDC42 Localizes to Manchette, HTCA and Tail and Interacts With ODF1 and ODF2 in the Formation of the Male Germ Cell Cytoskeleton[J]. Front Cell Dev Biol, 2019, 7:151. doi: 10.3389/fcell.2019.00151. doi: 10.3389/fcell.2019.00151 URL
[45]	Liu Y, Zhang L, Li W, et al. The sperm-associated antigen 6 interactome and its role in spermatogenesis[J]. Reproduction, 2019, 158(2):181-197. doi: 10.1530/REP-18-0522. doi: 10.1530/REP-18-0522
[46]	Pleuger C, Lehti MS, Cooper M, et al. CBE1 Is a Manchette- and Mitochondria-Associated Protein With a Potential Role in Somatic Cell Proliferation[J]. Endocrinology, 2019, 160(11):2573-2586. doi: 10.1210/en.2019-00468. doi: 10.1210/en.2019-00468
[47]	Tapia Contreras C, Hoyer-Fender S. The WD40-protein CFAP52/WDR16 is a centrosome/basal body protein and localizes to the manchette and the flagellum in male germ cells[J]. Sci Rep, 2020, 10(1):14240. doi: 10.1038/s41598-020-71120-9. doi: 10.1038/s41598-020-71120-9 URL