C-Src and c-Yes are two unlikely partners of spermatogenesis and their roles in blood-testis barrier dynamics

Src family kinases (SFKs), in particular c-Src and c-Yes, are nonreceptor protein tyrosine kinases that mediate integrin signaling at focal adhesion complex at the cell-extracellular matrix interface to regulate cell adhesion, cell cycle progression, cell survival, proliferation and differentiation, most notably in cancer cells during tumorigenesis and metastasis. Interestingly, recent studies have shown that these two proto-oncogenes are integrated components of the stem cell niche and the cell-cell actin-based anchoring junction known as ectoplasmic specialization (ES) at the: (1) Sertoli cell-spermatid interface known as apical ES and (2) Sertoli-Sertoli cell interface known as basal ES which together with tight junctions (TJ), gap junctions and desmosomes constitute the blood-testis barrier (BTB). At the stem cell niche, these SFKs regulate spermatogonial stem cell (SSC) renewal to maintain the proper population of SSC/spermatogonia for spermatogenesis. At the apical ES and the BTB, c-Src and c-Yes confer cell adhesion either by maintaining the proper phosphorylation status of integral membrane proteins at the site which in turn regulates protein-protein interactions between integral membrane proteins and their adaptors, or by facilitating androgen action on spermatogenesis via a nongenomic pathway which also modulates cell adhesion in the seminiferous epithelium. Herein, we critically evaluate recent findings in the field regarding the roles of these two unlikely partners of spermatogenesis. We also propose a hypothetical model on the mechanistic functions of c-Src and c-Yes in spermatogenesis so that functional experiments can be designed in future studies.