Li J C, Mruk D, Cheng C Y
Population Council, Center for Biomedical Research, New York, New York 10021, USA.
J Androl. 2001 Sep-Oct;22(5):847-56.
The timely opening and closing of inter-Sertoli cell tight junctions in the rat testis are essential cellular events in the completion of spermatogenesis. They permit the passage of preleptotene and leptotene spermatocytes to cross the blood-testis barrier from the basal compartment to the adluminal compartment of the seminiferous epithelium so that these cells can continue their further development into spermatids. However, the mechanism by which these events is regulated remains a mystery in male reproductive physiology. As part of our long-term goal of understanding the biology of this event and its regulation, transepithelial electrical resistance (TER) across the Sertoli cell epithelia when inter-Sertoli tight junctions were being assembled in vitro was quantified to assess the effects of different inhibitors of phosphatases and kinases on the inter-Sertoli tight junction permeability barrier. It was shown that inhibitors of protein tyrosine phosphatases (PTPi) and inhibitors of protein Ser/Thr phosphatases (PPi) could perturb the assembly and maintenance of the inter-Sertoli tight junction permeability barrier. Moreover, the inhibitory effects of PTPi were abolished by pretreating Sertoli cells with protein tyrosine kinase inhibitor (PTKi), which illustrates the specificity of the PTPi treatment. A cyclic adenosine monophosphate-dependent protein kinase A (PKA) activator and inhibitors of calcium-diacylglycerol-dependent protein kinase C (PKC) can also perturb the inter-Sertoli tight junction permeability barrier, which suggests that opening and closing of the inter-Sertoli tight junctions during spermatogenesis is likely regulated, at least in part, by the PKA/PKC pathways. Needless to say, these results illustrate that the interplay of protein kinases and phosphatases, which regulate the intracellular phosphoprotein content of Sertoli cells possibly via PKA and PKC signal transduction pathways, plays a crucial role in modulating the assembly and maintenance of inter-Sertoli tight junctions in the testis.
大鼠睾丸中支持细胞间紧密连接的适时开放和关闭是精子发生过程中至关重要的细胞事件。它们允许前细线期和细线期精母细胞穿过血睾屏障，从生精上皮的基底室进入管腔室，以便这些细胞能够继续进一步发育成精子细胞。然而，这些事件的调节机制在男性生殖生理学中仍然是个谜。作为我们理解这一事件及其调节生物学的长期目标的一部分，在体外组装支持细胞间紧密连接时，对穿过支持细胞上皮的跨上皮电阻（TER）进行了量化，以评估不同磷酸酶和激酶抑制剂对支持细胞间紧密连接通透性屏障的影响。结果表明，蛋白酪氨酸磷酸酶抑制剂（PTPi）和蛋白丝氨酸/苏氨酸磷酸酶抑制剂（PPi）会干扰支持细胞间紧密连接通透性屏障的组装和维持。此外，用蛋白酪氨酸激酶抑制剂（PTKi）预处理支持细胞可消除PTPi的抑制作用，这说明了PTPi处理的特异性。环磷酸腺苷依赖性蛋白激酶A（PKA）激活剂和钙-二酰甘油依赖性蛋白激酶C（PKC）抑制剂也会干扰支持细胞间紧密连接通透性屏障，这表明精子发生过程中支持细胞间紧密连接的开放和关闭可能至少部分受PKA/PKC途径调节。不用说，这些结果表明，蛋白激酶和磷酸酶之间的相互作用可能通过PKA和PKC信号转导途径调节支持细胞的细胞内磷蛋白含量，在调节睾丸中支持细胞间紧密连接的组装和维持方面起着关键作用。
