Oncotarget

Research Papers:

F5-peptide induces aspermatogenesis by disrupting organization of actin- and microtubule-based cytoskeletons in the testis

Ying Gao, Dolores D. Mruk, Wing-yee Lui, Will M. Lee and C. Yan Cheng _

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Oncotarget. 2016; 7:64203-64220. https://doi.org/10.18632/oncotarget.11887

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Abstract

Ying Gao1, Dolores D. Mruk1, Wing-yee Lui2, Will M. Lee2, C. Yan Cheng1

1The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, USA

2School of Biological Sciences, The University of Hong Kong, Hong Kong, China

Correspondence to:

C. Yan Cheng, email: Y-Cheng@popcbr.rockefeller.edu, ccheng@rockefeller.edu

Keywords: testis, F5-peptide, ectoplasmic specialization, actin cytoskeleton, microtubule cytoskeleton

Received: June 14, 2016     Accepted: August 29, 2016     Published: September 07, 2016

ABSTRACT

During the release of sperm at spermiation, a biologically active F5-peptide, which can disrupt the Sertoli cell tight junction (TJ) permeability barrier, is produced at the site of the degenerating apical ES (ectoplasmic specialization). This peptide coordinates the events of spermiation and blood-testis barrier (BTB) remodeling at stage VIII of the epithelial cycle, creating a local apical ES-BTB axis to coordinate cellular events across the epithelium. The mechanism(s) by which F5-peptide perturbs BTB restructuring, and its involvement in apical ES dynamics remain unknown. F5-peptide, besides perturbing BTB integrity, was shown to induce germ cell release from the epithelium following its efficient in vivo overexpression in the testis. Overexpression of F5-peptide caused disorganization of actin- and microtubule (MT)-based cytoskeletons, mediated by altering the spatiotemporal expression of actin binding/regulatory proteins in the seminiferous epithelium. F5-peptide perturbed the ability of actin microfilaments and/or MTs from converting between their bundled and unbundled/defragmented configuration, thereby perturbing adhesion between spermatids and Sertoli cells. Since apical ES and basal ES/BTB are interconnected through the underlying cytoskeletal networks, this thus provides an efficient and novel mechanism to coordinate different cellular events across the epithelium during spermatogenesis through changes in the organization of actin microfilaments and MTs. These findings also illustrate the potential of F5-peptide being a male contraceptive peptide for men.


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