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.

PROJECT NARRATIVE All five testis-specific serine kinases (TSSKs) are classified as understudied kinases by the “Illuminating the Druggable Genome” (IDG) consortium. This proposal aims to establish class IIa HDACs as functional substrates of TSSKs during the process of sperm development. Researches along this direction may not only elucidate TSSK signaling pathway, but also provide novel drug targets for male infertility.