Speculative model of the role of Nef in the inhibition of membrane remodeling during phagocytosis in HIV-1–infected macrophages. VAMP3-positive recycling endosomes bearing TNFα and VAMP7-positive late endosomes are recruited and fuse with the plasma membrane, thus contributing to pseudopod extension and optimal phagosome formation. AP1, and in particular the cleaved form of the complex that is unable to bind to clathrin, was proposed to regulate the focal delivery of VAMP3- and TNFα-positive membranes. In this study, we show that Nef interacts via its LL motif with AP1, associated either with membranes or with the cleaved form of the protein in the cytosol. This in turn would impair the plasmalemmal recruitment of endomembranes bearing the VAMP3 and TNFα markers that are known to be essential for optimal phagocytosis, without affecting F-actin cup formation or VAMP7-positive compartment delivery.