The human WASP-interacting protein, WIP, activates the cell polarity pathway in yeast.
WIP, the Wiskott-Aldrich syndrome protein-interacting protein, is a human protein involved in actin polymerization and redistribution in lymphoid cells. The mechanism by which WIP reorganizes actin cytoskeleton is unknown. WIP is similar to yeast verprolin, an actin- and myosin-interacting protein required for polarized morphogenesis. To determine whether WIP and verprolin are functional homologues, we analyzed the function of WIP in yeast. WIP suppresses 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 actin binding domain and a putative profilin binding domain. Immunofluorescence localization of WIP in yeast cells reveals a pattern consistent with its function at the cortical sites of growth. Thus, like verprolin, WIP functions in yeast to link the polarity development pathway and the actin cytoskeleton to generate cytoskeletal asymmetry. A role for WIP in cell polarity provides a framework for unifying, under a common paradigm, distinct molecular defects associated with immunodeficiencies like Wiskott-Aldrich syndrome.
Vaduva
G
G
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Martinez-Quiles
N
N
Anton
I M
IM
Martin
N C
NC
Geha
R S
RS
Hopper
A K
AK
Ramesh
N
N
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000302:isolation & purification; D002451:Cell Compartmentation; D016764:Cell Polarity / Q000235:genetics*; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D051304:Profilins; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D014923:Wiskott-Aldrich Syndrome; D015003:Yeasts
D002352:Carrier Proteins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; D051304:Profilins; D029701:Saccharomyces cerevisiae Proteins; C090350:VRP1 protein, S cerevisiae; C109903:WIPF1 protein, human