Fig. 11. Model for the role of the p95 complex in membrane recycling from the endocytic compartment. P95-APP1 interacts with PIX which in turn interacts with PAK. Moreover, the C-terminal portion of p95-APP1 can interact with paxillin, and induce paxillin relocalization away from focal adhesions. Both PIX and the ankyrin repeats of p95-APP1 may induce recruitment of the p95 complex to the endosomal compartment. In particular, PIX is required for the recruitment to Rab11-positive recycling endosomes (R.E.). Internalized membrane can normally be recycled back to the plasma membrane (PM) from the Rab11-positive recycling compartment. According to this model, the lack of a functional ARF-GAP domain may interfere with membrane recycling by preventing ARF-mediated vesicle budding from the recycling compartment, thus inducing an abnormal accumulation of large Rab11-positive vesicles. By contrast, activation of Rac at the cell surface may induce translocation of the p95 complex, and possibly of recycling vesicles, to the cell surface via the interaction with the Rac effector PAK. This would result in the transport to the cell periphery of new focal adhesion components (paxillin) and of part of the machinery required for Rac-mediated actin assembly (PAK, PIX). See text for more details.