Figure 3.

A hypothetical model that summarizes the mechanism by which adjudin induces spermatid loss from the seminiferous epithelium of adult rat testes. In a normal rat testis (A), apical ES adhesion is maintained by the apical ES adhesion protein complexes (e.g., α6β1-integrin-laminin-α3β3γ3, N-cadherin-β-catenin, nectin-2/3-afadin) using the highly organized actin filament bundles for attachment. The actin filament bundles at the apical ES are maintained by the Eps8, PAR6 and 14-3-3. However, following exposure of rats to adjudin, this drug disrupts the highly restricted temporal and spatial expression of Eps8, Arp3, drebrin E, PAR6 and 14-3-3 in the seminiferous epithelium as detailed in the text. In short, Eps8 considerably diminishes at the apical ES with a concomitant mis-localization and truncation of Arp3, the actin filament bundles thus become disrupted and replaced with actin branched network. At the same time, PAR6 and 14-3-3 also become diminished, accelerating endocytic vesicle-mediated internalization of integral membrane proteins (e.g., integrins, cadherins, nectins), thereby destabilizing the apical ES (B), which eventually leads to the premature loss of spermatids from the epithelium, mimicking spermiation as shown in (C).