New insights into FAK function and regulation during spermatogenesis.
New insights into FAK function and regulation during spermatogenesis.
复制标题
DOI：
10.14670/hh-29.977
复制
发表时间：
2014-08
影响因子：
2
通讯作者：
Cheng CY
中科院分区：
文献类型：
--
作者：
Gungor-Ordueri NE;Mruk DD;Wan HT;Wong EW;Celik-Ozenci C;Lie PP;Cheng CY
在上皮周期期间，生殖细胞穿过生精上皮的运输对于精子发生至关重要，尽管调节这些事件的分子机制仍然未知。研究表明，上皮周期期间关键调节蛋白的时空表达代表了调节精子发生的有效且生理学上重要的机制，而不涉及蛋白质的从头合成和/或基因的表达。在此，我们批判性地回顾了粘着斑激酶（FAK）在精子发生过程中沿着顶端外质特化（ES）-血睾屏障-基底膜（BM）功能轴分别协调精子细胞和前细线精母细胞穿过上皮和血睾屏障（BTB）的运输中的作用。在睾丸中，p-FAK-Tyr397 和 p-FAKTyr407 在上皮周期期间在富含肌动蛋白的锚定连接（称为 ES）处时空表达，调节支持细胞（顶端 ES）和支持细胞-细胞（基底 ES）界面的细胞粘附。 FAK 的磷酸化形式通过调节 ES 处 F-肌动蛋白的稳态来发挥作用，通过其对肌动蛋白聚合的影响进行介导，从而使微丝有效地重组，例如在上皮周期期间从“捆绑”构型变为“解捆绑/分支”构型，反之亦然，以促进以下物质的运输：（i）精细胞穿过上皮，以及（ii）前细线精母细胞穿过 BTB。总之，p-FAK-Tyr407 和 p-FAK-Tyr397 是精子发生的重要调节因子，它们作为分子开关，通过其在上皮周期期间的时空表达介导“打开”和“关闭”顶端 ES 和基底 ES/BTB 的粘附功能。还提出了描述这两种分子开关作用的假设模型。
Germ cell transport across the seminiferous epithelium during the epithelial cycle is crucial to spermatogenesis, although molecular mechanism(s) that regulate these events remain unknown. Studies have shown that spatiotemporal expression of crucial regulatory proteins during the epithelial cycle represents an efficient and physiologically important mechanism to regulate spermatogenesis without involving de novo synthesis of proteins and/or expression of genes. Herein, we critically review the role of focal adhesion kinase (FAK) in coordinating the transport of spermatids and preleptotene spermatocytes across the epithelium and the blood-testis barrier (BTB), respectively, along the apical ectoplasmic specialization (ES) – blood-testis barrier – basement membrane (BM) functional axis during spermatogenesis. In the testis, p-FAK-Tyr397 and p-FAKTyr407 are spatiotemporally expressed during the epithelial cycle at the actin-rich anchoring junction known as ES, regulating cell adhesion at the Sertolispermatid (apical ES) and Sertoli cell-cell (basal ES) interface. Phosphorylated forms of FAK exert their effects by regulating the homeostasis of F-actin at the ES, mediated via their effects on actin polymerization so that microfilaments are efficiently re-organized, such as from their “bundled” to “de-bundled/branched” configuration and vice versa during the epithelial cycle to facilitate the transport of: (i) spermatids across the epithelium, and (ii) preleptotene spermatocytes across the BTB. In summary, p-FAK-Tyr407 and p-FAK-Tyr397 are important regulators of spermatogenesis which serve as molecular switches that turn “on” and “off” adhesion function at the apical ES and the basal ES/BTB, mediated via their spatiotemporal expression during the epithelial cycle. A hypothetical model depicting the role of these two molecular switches is also proposed.