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Abstract

Regulation of Sertoli cell myotubularin (rMTM) expression by germ cells in vitro (PDF) (HTML) 
Li,Jonathan C.H.; Lee,William M.; Mruk,Dolores D.; Cheng,Chuen-yan
Journal of Andrology 22(2): 266-277
Publication date: 2001

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Recent studies have shown that rat myotubularin (rMTM), the homolog ofhuman myotubularin, which is a putative protein tyrosine phosphatase (PTP),is expressed by Sertoli cells in the rat testis. In addition, a significantincrease in its steady-state mRNA level was detected in Sertoli cells atthe time of inter-Sertoli tight junction (TJ) assembly in vitro. Since theinterplay of protein kinases and phosphatases that determines theintracellular phosphoprotein content can, in turn, regulate the assemblyand maintenance of TJ and anchoring junctions (AJ) in vitro, asdemonstrated in different cell types, such as Madin-Darby canine kidney(MDCK) cells, endothelial cells, and Sertoli cells, rMTM may be animportant molecule in regulating the assembly and maintenance ofinter-Sertoli TJs during spermatogenesis. We thus sought to characterizeits regulation. During testicular maturation, it was shown that the rMTMsteady-state mRNA level increased drastically with aging. The expression ofrMTM increased by as much as 2-4-fold in the rat testis at 45-60 days ofage versus 20 days of age, coinciding with the onset of spermiation. Thisresult seemingly suggests that rMTM may participate in the release ofspermatids by disassembling the Sertoli-spermatid AJs, since PTP inhibitorwas shown to perturb the inter-Sertoli TJ permeability barrier in vitro.Unexpectedly, when Sertoli cells were isolated from 20-, 45-, and90-day-old rats and the steady-state rMTM level was quantified, it wasshown that there is a drastic reduction in rMTM expression in adult Sertolicells. Studies that used Sertoli-germ cell cocultures and Sertoli cellsincubated with increasing germ cell-derived proteins have shown that thehigh level of testicular rMTM expression in the testis might be maintainedby germ cells. Although work remains to be done to delineate the role ofrMTM in the testis, these results illustrate that germ cells play a veryactive role in regulation testicular function by altering thephosphoprotein content.

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