The human WASP-interacting protein, WIP, activates the cell polarity pathway in yeast

WIP, the Wiskott-Aldrich syndrome protein-interacting protein, is a human p rotein involved in actin polymerization and redistribution in lymphoid cell s. The mechanism by which WIP reorganizes actin cytoskeleton is unknown. WI P is similar to yeast verprolin, an actin- and myosin-interacting protein r equired for polarized morphogenesis. To determine whether WIP and verprolin are functional homologues, we analyzed the function of WIP in yeast. WIP s uppresses the growth defects of VRP1 missense and null mutations as well as the defects in cytoskeletal organization and endocytosis observed in vrp1- 1 cells. The ability of WIP to replace verprolin is dependent on its WH2 ac tin binding domain and a putative profilin binding domain. Immunofluorescen ce localization of WIP in yeast cells reveals a pattern consistent with its function at the cortical sites of growth. Thus, like verprolin, WIP functi ons in yeast to link the polarity development pathway and the actin cytoske leton to generate cytoskeletal asymmetry. A role for WIP in cell polarity p rovides a framework for unifying, under a common paradigm, distinct molecul ar defects associated with immunodeficiencies like Wiskott-Aldrich syndrome .