Phagocytosis is a remarkably complex and versatile process: it contributes to innate immunity through the ingestion and elimination of pathogens, while also being central to tissue homeostasis and remodeling by clearing effete cells. The ability of phagocytes to perform such diverse functions rests, in large part, on their vast repertoire of receptors. In this review, we address the various receptor types, their mobility in the plane of the membrane, and two modes of receptor crosstalk: priming and synergy. A major section is devoted to the actin cytoskeleton, which not only governs receptor mobility and clustering but also is instrumental in particle engulfment. Four stages of the actin remodeling process are identified and discussed: (i) the 'resting' stage that precedes receptor engagement, (ii) the disruption of the cortical actin prior to formation of the phagocytic cup, (iii) the actin polymerization that propels pseudopod extension, and (iv) the termination of polymerization and removal of preassembled actin that are required for focal delivery of endomembranes and phagosomal sealing. These topics are viewed in the larger context of the differentiation and polarization of the phagocytic cells.

Peroxisomes and the ER exchange lipids for various metabolic and anabolic reactions. In this study, Hua et al. show that the interaction between the ER-resident VAPs with the peroxisomal protein ACBD5 tethers peroxisomes to the ER. This tether is required for the exchange of lipids, including cholesterol, between the two organelles.

WAVE2 is a member of the Wiskott-Aldrich syndrome protein family of cytoskeletal regulatory proteins shown to link Rac activation to actin remodeling via induction of Arp 2͞3 activity. WAVE2 is thought to be regulated by its positioning in a macromolecular complex also containing the Abelson-(Abl) interactor-1 (Abi-1) adaptor, but the molecular basis and biologic relevance of WAVE2 inclusion in this complex are ill defined. Here we show that Abi-1 binding to WAVE2 is mediated by discrete motifs in the Abi-1 coiled-coil and WAVE2 WAVE-homology domains and increases markedly in conjunction with Abi-1-WAVE2 translocation and colocalization at the leading edge in B16F1 cells after fibronectin stimulation. Abi-1 also couples WAVE2 to Abl after cell stimulation, an interaction that triggers Abl membrane translocation with WAVE2, Abi-1, and activated Rac, as well as Abl-mediated tyrosine phosphorylation and WAVE2 activation. By contrast, mutation of tyrosine residue Y150, identified here as the major site of Ablmediated WAVE2 tyrosine phosphorylation, as well as disruption of WAVE2-Abi-1 binding, impairs induction of WAVE2-driven actin polymerization and its membrane translocation in association with activated Rac. Similarly, WAVE2 tyrosine phosphorylation and induction of membrane actin rearrangement are abrogated in fibroblasts lacking the Abl family kinase. Together, these data reveal that Abi-1-mediated coupling of Abl to WAVE2 promotes Abl-evoked WAVE2 tyrosine phosphorylation required to link WAVE2 with activated Rac and with actin polymerization and remodeling at the cell periphery.actin polymerization ͉ cytoskeletal dynamics ͉ WASp family T he actin cytoskeleton is a dynamic structure integrally involved in the coupling of extracellular stimuli to cell activation and concomitant changes in morphology, motility, and many other fundamental cellular processes. Among the many effectors involved in poststimulatory actin-based cellular responses, members of the Wiskott-Aldrich syndrome protein (WASp) family are now recognized as particularly important players in connecting stimulatory signals to actin cytoskeletal reorganization. In addition to WASp, this family includes the WASp ortholog, N-WASp, and, in mammalian cells, three WAVE͞SCAR isoforms, WAVEs 1, 2, and 3 (1-3). All of these cytosolic proteins contain a C-terminal verprolin homology͞connecting region͞acidic region (VCA) domain, which mediates binding to actin monomers and the Arp 2͞3 complex and consequent induction of Arp 2͞3 actin nucleating activity (4). Immediately upstream of the VCA domain, the WASp family members all contain a proline-rich region that mediates interaction with profilin and SH3 domain-containing proteins, the latter of which modulate subcellular location and possibly activation of WASp͞N-WASp (5-7). WASp and N-WASp also contain an N-terminal EVH1 and cdc42͞Rac interactive binding domain, which respectively mediate interactions with the WASp-interacting protein and the activated form of the Rho family GTPase, cdc42 (8, 9). WASp͞N-WASp ...