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Research Papers:

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

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

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Oncotarget. 2017; 8:58430-58442. https://doi.org/10.18632/oncotarget.16915

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Abstract

Di Wu1, Chun-Jie Huang1, Faheem Ahmed Khan1, Xiao-Fei Jiao1, Xiao-Ming Liu2, Nuruliarizki Shinta Pandupuspitasari3, Rahim Dad Brohi1 and Li-Jun Huo1

1Key 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

2Second Affiliated Hospital and Center of Reproductive Medicine, The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

3The Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, Hubei, China

Correspondence to:

Li-Jun Huo, email: lijunhuo@yahoo.com

Keywords: SUMOylation, Sertoli cell, tight junction, cytoskeleton, blood-testis barrier

Abbreviations: SENP3, sentrin/SUMO-specific proteases 3; BTB, blood-testis barrier; TJ, tight junction; basal ES, basal ectoplasmic specializations; TER, trans-epithelial electrical resistance

Received: December 06, 2016     Accepted: March 14, 2017     Published: April 07, 2017

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.


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