TSSK-dependent signaling pathway in spermatogenesis

摘要 睾丸特异性丝氨酸激酶（Testis-specific serine kinases，TSSKs）属于AMPK相关激酶家族。一些功能丧失突变体 TSSK成员导致雄性小鼠精子发生缺陷，TSSK的几个SNP与 男性不育症然而，TSSK在精子发生过程中的信号转导机制尚不清楚。 本研究以果蝇为模型系统，研究一种新的激酶-底物对：TSSKs类 IIa HDAC。目的1将使用生物化学和生物化学方法确定IIa类HDAC是否是TSSK的底物。 基因方法。目的2将探索TSSK IIa类HDAC在治疗期间的功能相关性。 果蝇精子发生总的来说，该提案将把IIa类HDAC作为关键的下游 TSSK信号的组成部分。

ABSTRACT Testis-specific serine kinases (TSSKs) belong to AMPK-related kinase family. Loss-of-function mutants of some TSSK members lead to spermatogenesis defects in male mice, and several SNPs of TSSKs are associated with male infertility in humans. However, the TSSK signaling mechanism during spermatogenesis is not understood. This proposal employs Drosophila as a model system to investigate a novel kinase-substrate pair: TSSKs-class IIa HDACs. Aim 1 will determine whether class IIa HDACs are substrates of TSSKs using both biochemical and genetic approaches. Aim 2 will explore the functional relevance of TSSKs-class IIa HDACs during spermatogenesis in Drosophila. Collectively, this proposal will establish class IIa HDACs as the key downstream component of TSSK signaling.