威斯科特-奥尔德里奇综合征蛋白调节原代人巨噬细胞中的足体。
Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages.
作者信息
Linder S, Nelson D, Weiss M, Aepfelbacher M
机构信息
Max von Pettenkofer-Institut für Medizinische Mikrobiologie, Pettenkoferstrasse 9a, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
出版信息
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9648-53. doi: 10.1073/pnas.96.17.9648.
Wiskott-Aldrich syndrome protein (WASp) is a hematopoietic-specific, multidomain protein whose mutation is responsible for the immunodeficiency disorder Wiskott-Aldrich syndrome. WASp contains a binding motif for the Rho GTPase CDC42Hs as well as verprolin/cofilin-like actin-regulatory domains, but no specific actin structure regulated by CDC42Hs-WASp has been identified. We found that WASp colocalizes with CDC42Hs and actin in the core of podosomes, a highly dynamic adhesion structure of human blood-derived macrophages. Microinjection of constitutively active V12CDC42Hs or a constitutively active WASp fragment consisting of the verprolin/cofilin-like domains led to the disassemly of podosomes. Conversely, macrophages from patients expressing truncated forms of WASp completely lacked podosomes. These findings indicate that WASp controls podosome assembly and, in cooperation with CDC42Hs, podosome disassembly in primary human macrophages.
威斯科特-奥尔德里奇综合征蛋白（WASp）是一种造血特异性的多结构域蛋白，其突变会导致免疫缺陷疾病威斯科特-奥尔德里奇综合征。WASp包含一个与Rho GTP酶CDC42Hs结合的基序以及维普洛林/丝切蛋白样肌动蛋白调节结构域，但尚未鉴定出由CDC42Hs-WASp调节的特定肌动蛋白结构。我们发现，WASp与CDC42Hs和肌动蛋白在足体核心中共定位，足体是人类血液来源巨噬细胞的一种高度动态的粘附结构。显微注射组成型活性V12CDC42Hs或由维普洛林/丝切蛋白样结构域组成的组成型活性WASp片段会导致足体解体。相反，表达截短形式WASp的患者的巨噬细胞完全缺乏足体。这些发现表明，WASp控制足体组装，并与CDC42Hs协同控制原代人类巨噬细胞中的足体解体。
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