Functional characterization of SPATC1L with testis-specific expression.

Abstract

Spermatogenesis is a tightly regulated process involving germ cell-specific and -predominant genes. Here we investigate a novel germ cell-specific gene, Spatc1l (spermatogenesis and centriole associated 1 like), previously identified from the mouse round spermatid UniGene library. Expression analyses show that SPATC1L is expressed as a 38-kDa protein in mouse and human testes. Mouse SPATC1L was found to localize to the neck region in testicular sperm. Proteomic analysis revealed that SPATC1L is associated with the regulatory subunit of protein kinase A (PKA) in male germ cells and increases PKA activity. Using CRISPR/Cas9-mediated genome engineering, mice lacking SPATC1L were generated. Disruption of Spatc1l in mice leads to male sterility owing to separation of sperm heads from tails. The lack of SPATC1L is associated with a reduction in PKA activity in testicular sperm and we identify CAPZB (capping protein muscle Z-line beta) as a candidate target of phosphorylation by PKA in testis. Taken together, these results implicate the SPATC1L-PKA complex in maintaining the stability of the sperm head-tail junction, thereby revealing a new molecular basis for sperm head-tail integrity.