Figure 2.

A schematic illustration of the current concepts of mechanism by which adjudin perturbs apical ES function in the seminiferous epithelium to induce germ cell loss from the seminiferous epithelium. During spermatogenesis, such as in the seminiferous epithelium of a stage VII tubule (left panel), the expression of EPS8 is high at the apical ES for the maintenance of F-actin organization via its actin bundling activity to stabilize that apical ES. The integrity of the apical ES in this stage VII tubule is also maintained via an elevated expression of p-FAK-Tyr³⁹⁷, perhaps being used to maintain the proper phosphorylation status of the constituent proteins at the apical ES (Siu et al. 2003), as well as to recruit additional adaptors (e.g. p130 Cas, vinculin) to the site to reinforce cell adhesion (Siu & Cheng 2008). As spermatogenesis proceeds (lower panel), ARP3, whose expression is also high at the apical ES in stage VII (Lie et al. 2010), causes ‘debundling’ of actin filaments by promoting actin branching. At the same time, endocytosis facilitates recycling of apical ES proteins for the assembly of ‘new’ apical ES that arises via spermiogenesis such as newly formed step 8 spermatids (Cheng & Mruk 2010b). At stage VIII of the seminiferous epithelial cycle when spermiation occurs, the apical ES is destabilized as the result of ‘debundling’ of actin filament due to the down-regulation of EPS8 with concomitant actin branching promoted by ARP3 (Lie et al. 2009b, 2010). On the other hand, new apical ES is being assembled for developing step 8–9 spermatids, such as via protein transcytosis and/or de novo synthesis of ‘new’ apical ES proteins. When rats are treated with adjudin (right panel), the above-described events, which only take place for step 18–19 spermatids during stage VII–VIII tubule, are ‘triggered’ to occur ‘prematurely’ at the apical ES in other stages of tubules with step 8–19 spermatids. Therefore, spermiation takes place ‘prematurely’ in developing spermatids in other staged tubules besides stage VIII. In addition, p-FAK-Tyr³⁹⁷ is highly expressed at the apical ES for the induction of the integrin/FAK/PI3-kinase/p130Cas/MAP kinase signaling pathway (Siu et al. 2003) to further destabilize apical ES to cause ‘premature’ spermiation in spermatids from steps 8 to 19.