Figure 4. A schematic model illustrating the role of non-receptor protein tyrosine kinases such as c-Yes and FAK on spermatid transport utilizing apical ES during the epithelial cycle.

The left panel illustrates the status of the apical ES from late to early stage VIII of the epithelial cycle in which p-FAK-Tyr⁴⁰⁷ recruits (likely mediated by drebrin [116]) and activates the barbed end actin nucleation protein Arp3 [40]. This effectively converts actin filaments from “bundled” to “unbundled/branched” configuration, thereby destabilizing the apical ES adhesion proteins beginning at the concave side of the spermatid head. This also facilitates endocytic vesicle-mediated trafficking events, such as endocytosis, transcytosis and recycling so that “old” apical ES proteins can be re-used to assemble “new” apical ES when step 8 spermatids appear in stage VIII of the cycle [38, 44]. On the convex side of the spermatid head, the apical ES function is maintained by p-FAK-Tyr³⁹⁷ which recruits Eps8 and palladin to confer actin microfilaments in their bundled configuration [48]. In late stage VIII when the expression of Eps8 and palladin are considerably diminished, actin filaments can no longer be maintained to confer apical ES function. Furthermore, matrix metalloprotease-2 (MMP-2) induces proteolytic cleavage of laminin chains to generate biologically active fragments, such as laminin-γ3 domain IV, which can induce BTB restructuring [51, 52, 117]. As such, the events of spermiation and BTB restructuring that take place simultaneously at stage VIII of the epithelial cycle are coordinated.