TSSK-dependent signaling pathway in spermatogenesis

摘要 睾丸特异性丝氨酸激酶(TSSKs)属于AMPK相关激酶家族。一些功能缺失的突变体 TSSK成员导致雄性小鼠精子发生缺陷，TSSK的几个SNPs与 人类中的男性不育。然而，精子发生过程中的TSSK信号机制尚不清楚。 该方案使用果蝇作为模型系统来研究一种新的激酶-底物对：TSSKs类 IIa HDAC。目标1将确定IIa类HDAC是否为TSSK的底物，使用生化和 遗传方法。目标2将探讨TSSKs-Class IIa HDAC在 果蝇的精子发生。总的来说，这项提议将建立IIa类HDAC作为关键的下游 TSSK信令的组件。

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.