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14-3-3 Protein Regulates Cell Adhesion in the Seminiferous Epithelium of Rat Testes

Center for Biomedical Research (E.W.P.W., S.S., M.W.M.L., C.Y.C.), Population Council, New York, New York 10065; and School of Biological Sciences (W.M.L.), The University of Hong Kong, Hong Kong, China

Address all correspondence and requests for reprints to: C. Yan Cheng, Ph.D., The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, New York 10065. E-mail: y-cheng{at}popcbr.rockefeller.edu.

Polarity proteins have been implicated in regulating and maintaining tight junction (TJ) and cell polarity in epithelia. Here we report 14-3-3, the homolog of Caenorhabditis elegans Par5 in mammalian cells, which is known to confer cell polarity at TJ, is found at the apical ectoplasmic specialization (ES), a testis-specific adherens junction type restricted to the Sertoli cell-elongating spermatid interface, in which TJ is absent. 14-3-3 was shown to play a critical role in conferring cell adhesion at the apical ES. A loss of 14-3-3 expression at the apical ES was detected in the seminiferous epithelium before spermiation. Involvement of 14-3-3 in Sertoli cell adhesion was confirmed by its knockdown by RNA interference in Sertoli cells cultured in vitro with established TJ permeability barrier that mimicked the blood-testis barrier (BTB) in vivo. Mislocalization of N-cadherin and zonula occludens-1, but not - and β-catenins, was observed after 14-3-3 knockdown in Sertoli cells, moving from the cell-cell interface to cytosol, indicating a disruption of cell adhesion. Studies by endocytosis assay illustrated that this loss of cell adhesion was mediated by an increase in the kinetics of endocytosis of N-cadherin and junctional adhesion molecule-A at the BTB, which may represent a general mechanism by which polarity proteins regulate cell adhesion. In summary, the testis is using 14-3-3 to regulate cell adhesion at the apical ES to facilitate spermiation and at the BTB to facilitate the transit of preleptotene spermatocytes at stages VIII–IX of the epithelial cycle. 14-3-3 may act as a molecular switch that coordinates these two cellular events in the seminiferous epithelium during spermatogenesis.