Vaduva G, Martinez-Quiles N, Anton I M, Martin N C, Geha R S, Hopper A K, Ramesh N
Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
J Biol Chem. 1999 Jun 11;274(24):17103-8. doi: 10.1074/jbc.274.24.17103.
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.
WIP，即威斯科特-奥尔德里奇综合征蛋白相互作用蛋白，是一种参与淋巴细胞中肌动蛋白聚合和重新分布的人类蛋白。WIP重组肌动蛋白细胞骨架的机制尚不清楚。WIP与酵母中的verprolin相似，后者是极化形态发生所需的一种与肌动蛋白和肌球蛋白相互作用的蛋白。为了确定WIP和verprolin是否为功能同源物，我们分析了WIP在酵母中的功能。WIP可抑制VRP1错义突变和无效突变导致的生长缺陷，以及在vrp1-1细胞中观察到的细胞骨架组织和内吞作用缺陷。WIP替代verprolin的能力取决于其WH2肌动蛋白结合结构域和一个假定的脯氨酰肌动蛋白结合蛋白结合结构域。WIP在酵母细胞中的免疫荧光定位揭示了一种与其在生长皮质位点的功能一致的模式。因此，与verprolin一样，WIP在酵母中发挥作用，将极性发育途径与肌动蛋白细胞骨架联系起来以产生细胞骨架不对称性。WIP在细胞极性中的作用为在一个共同范式下统一与威斯科特-奥尔德里奇综合征等免疫缺陷相关的不同分子缺陷提供了一个框架。
