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Abstract

14-3-3 protein regulates cell adhesion in the seminiferous epithelium of rat testes 
Wong,Elissa W.P.; Sun,Shengyi; Li,Michelle W.M.; Lee,Will M.; Cheng,Chuen-yan
Endocrinology 150(10): 4713-4723
Publication date: 2009


Polarity proteins have been implicated in regulating and maintainingtight junction (TJ) and cell polarity in epithelia. Here wereport 14-3-3, the homolog of Caenorhabditis elegans Par5 inmammalian cells, which is known to confer cell polarity at TJ,is found at the apical ectoplasmic specialization (ES), a testis-specificadherens junction type restricted to the Sertoli cell-elongatingspermatid interface, in which TJ is absent. 14-3-3 was shownto play a critical role in conferring cell adhesion at the apicalES. A loss of 14-3-3 expression at the apical ES was detectedin the seminiferous epithelium before spermiation. Involvementof 14-3-3 in Sertoli cell adhesion was confirmed by its knockdownby RNA interference in Sertoli cells cultured in vitro withestablished TJ permeability barrier that mimicked the blood-testisbarrier (BTB) in vivo. Mislocalization of N-cadherin and zonulaoccludens-1, but not - and ß-catenins, was observed after14-3-3 knockdown in Sertoli cells, moving from the cell-cellinterface to cytosol, indicating a disruption of cell adhesion.Studies by endocytosis assay illustrated that this loss of celladhesion was mediated by an increase in the kinetics of endocytosisof N-cadherin and junctional adhesion molecule-A at the BTB,which may represent a general mechanism by which polarity proteinsregulate cell adhesion. In summary, the testis is using 14-3-3to regulate cell adhesion at the apical ES to facilitate spermiationand at the BTB to facilitate the transit of preleptotene spermatocytesat stages VIII-IX of the epithelial cycle. 14-3-3 mayact as a molecular switch that coordinates these two cellularevents in the seminiferous epithelium during spermatogenesis.