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Abstract

The inter-Sertoli tight junction permeability barrier is regulated by the interplay of protein phosphatases and kinases: An in vitro study 
Li,Jonathan C.H.; Mruk,Dolores D.; Cheng,Chuen-yan
Journal of Andrology 22(5): 847-856
Publication date: 2001


The timely opening and closing of inter-Sertoli cell tight junctions in therat testis are essential cellular events in the completion ofspermatogenesis. They permit the passage of preleptotene and leptotenespermatocytes to cross the blood-testis barrier from the basal compartmentto the adluminal compartment of the seminiferous epithelium so that thesecells can continue their further development into spermatids. However, themechanism by which these events is regulated remains a mystery in malereproductive physiology. As part of our long-term goal of understanding thebiology of this event and its regulation, transepithelial electricalresistance (TER) across the Sertoli cell epithelia when inter-Sertoli tightjunctions were being assembled in vitro was quantified to assess theeffects of different inhibitors of phosphatases and kinases on theinter-Sertoli tight junction permeability barrier. It was shown thatinhibitors of protein tyrosine phosphatases (PTPi) and inhibitors ofprotein Ser/Thr phosphatases (PPi) could perturb the assembly andmaintenance of the inter-Sertoli tight junction permeability barrier.Moreover, the inhibitory effects of PTPi were abolished by pretreatingSertoli cells with protein tyrosine kinase inhibitor (PTKi), whichillustrates the specificity of the PTPi treatment. A cyclic adenosinemonophosphate-dependent protein kinase A (PKA) activator and inhibitors ofcalcium-diacylglycerol-dependent protein kinase C (PKC) can also perturbthe inter-Sertoli tight junction permeability barrier, which suggests thatopening and closing of the inter-Sertoli tight junctions duringspermatogenesis is likely regulated, at least in part, by the PKA/PKCpathways. Needless to say, these results illustrate that the interplay ofprotein kinases and phosphatases, which regulate the intracellularphosphoprotein content of Sertoli cells possibly via PKA and PKC signaltransduction pathways, plays a crucial role in modulating the assembly andmaintenance of inter-Sertoli tight junctions in the testis.