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SENP3维持小鼠支持细胞中的紧密连接完整性和细胞骨架结构。

SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

作者信息

Wu Di, Huang Chun-Jie, Khan Faheem Ahmed, Jiao Xiao-Fei, Liu Xiao-Ming, Pandupuspitasari Nuruliarizki Shinta, Brohi Rahim Dad, Huo Li-Jun

机构信息

Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, China.

Second Affiliated Hospital and Center of Reproductive Medicine, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.

出版信息

Oncotarget. 2017 Apr 7;8(35):58430-58442. doi: 10.18632/oncotarget.16915. eCollection 2017 Aug 29.

DOI:10.18632/oncotarget.16915
PMID:28938568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5601664/
Abstract

Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

摘要

生殖细胞在一个复杂的免疫特权微环境中发育，该微环境由与相邻支持细胞基底膜相邻的特殊连接提供，这些连接构成了哺乳动物睾丸生精上皮中的血睾屏障（BTB）。解读BTB活性的分子调控机制对于提高男性生育能力至关重要，包括SUMO化途径在内的翻译后修饰作用是关键因素之一。在此，我们揭开了SUMO-2/3特异性蛋白酶SENP3（Sentrin特异性蛋白酶3）在BTB动态调节中的奥秘。SENP3在成年小鼠睾丸的支持细胞和精母细胞的细胞核中大量表达，敲低SENP3会破坏支持细胞中的紧密连接，通过破坏初级支持细胞的通透性功能，同时伴随着跨上皮电阻的下降，这可能归因于细胞间界面处紧密连接（TJ）蛋白（如ZO-1、闭合蛋白）因STAT3失活而明显功能失调。此外，敲低SENP3会通过干预Rac1/CDC42-N-WASP-Arp2/3信号通路和丝切蛋白-1丰度来破坏支持细胞中的F-肌动蛋白结构。我们的研究指出，SENP3可能是调控哺乳动物睾丸中BTB动态的多种途径的新决定因素，以支持生殖细胞的发育。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/224ee6cbf6ee/oncotarget-08-58430-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/365720642eb4/oncotarget-08-58430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/79f80816a49a/oncotarget-08-58430-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/2a49cc42d40a/oncotarget-08-58430-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/ff6cb458fad5/oncotarget-08-58430-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/6f683f879405/oncotarget-08-58430-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/db2df0ed7248/oncotarget-08-58430-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/224ee6cbf6ee/oncotarget-08-58430-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/365720642eb4/oncotarget-08-58430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/79f80816a49a/oncotarget-08-58430-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/2a49cc42d40a/oncotarget-08-58430-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/ff6cb458fad5/oncotarget-08-58430-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/6f683f879405/oncotarget-08-58430-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/db2df0ed7248/oncotarget-08-58430-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/538d/5601664/224ee6cbf6ee/oncotarget-08-58430-g007.jpg

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