Myotubularin phosphoinositide phosphatases, protein phosphatases, and kinases: Their roles in junction dynamics and spermatogenesis
Zhang,Jiayi; Mruk,Dolores D.; Cheng,Chuen-yan
Journal of Cellular Physiology 204(2): 470-483
Publication date: 2005
Spermatogenesis in the seminiferous epithelium of the mammalian testis is a dynamic cellular event. It involves extensive restructuring at the Sertoli-germ cell interface, permitting germ cells to traverse the epithelium from basal to adluminal compartment. As such, Sertoli-germ cell actin-based adherens junctions (AJ), such as ectoplasmic specializations (ES), must disassemble and reassemble to facilitate this event. Recent studies have shown that AJ dynamics are regulated by intricate interactions between AJ integral membrane proteins (e.g., cadherins, a6b1 integrins and nectins), phosphatases, kinases, adaptors and the underlying cytoskeleton network. For instance, the myotubularin (MTM) phosphoinositide phosphatases, such as MTM related protein 2 (MTMR2), can form a functional complex with c-Src (a non-receptor protein tyrosine kinase). In turn, this phosphatase/kinase complex associates with b-catenin, a constituent of the N-cadherin/b-catenin functional unit at the AJ site. This MTMR2-c-Src-b-catenin complex apparently regulates the phosphorylation status of b-catenin, which determines cell adhesive function conferred by the cadherin-catenin protein complex in the seminiferous epithelium. In this review, we discuss the current status of research on selected phosphatases and kinases, and how these proteins potentially interact with adaptors at AJ in the seminiferous epithelium to regulate cell adhesion in the testis. Specific research areas that are open for further investigation are also highlighted.