A Coronin7 Homolog with Functions in Actin-driven Processes*

A Coronin7 Homolog with Functions in Actin-driven Processes*
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DOI:
10.1074/jbc.m109.083725
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发表时间:
2010-01
期刊:
The Journal of Biological Chemistry
影响因子:
--
通讯作者:
M. Shina;C. Ünal;L. Eichinger;A. Müller-Taubenberger;M. Schleicher;M. Steinert;A. Noegel
M. Shina;C. Ünal;L. Eichinger;A. Müller-Taubenberger;M. Schleicher;M. Steinert;A. Noegel
中科院分区:
其他
文献类型:
--
作者:
M. Shina;C. Ünal;L. Eichinger;A. Müller-Taubenberger;M. Schleicher;M. Steinert;A. Noegel

文献摘要

被引文献

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盘状网柄藻Coronin 7(DdCRN 7)与人Coronin 7(CRN 7)以及果蝇和秀丽隐杆线虫的Pod-1都属于含WD重复结构域的冠蛋白家族。Coronin 7蛋白质的特征在于两个WD重复结构域,其可能折叠成两个β螺旋桨结构。DdCRN 7与人CRN 7具有最高的同源性,CRN 7是一种在膜运输中起作用的蛋白质。DdCRN 7存在于胞质溶胶中,并在运动和吞噬和胞饮期间在细胞表面突起中积累。缺乏CRN 7的细胞具有改变的趋化性和吞噬作用。此外,CRN 7的缺失影响病原体嗜肺军团菌的感染过程,并允许细菌更有效的内化。为了提供CNR 7作用的机制,我们研究了肌动蛋白相关的方面。我们可以证明CRN 7直接与F-肌动蛋白结合,并保护肌动蛋白丝免于解聚。CRN 7在体内也与F-肌动蛋白相关。它存在于Triton X-100不溶性细胞骨架中,与F-肌动蛋白共定位,其分布对影响肌动蛋白细胞骨架的药物敏感。我们认为CRN 7在趋化和吞噬作用中的作用是通过其对肌动蛋白细胞骨架的影响。
Dictyostelium discoideum Coronin7 (DdCRN7) together with human Coronin7 (CRN7) and Pod-1 of Drosophila melanogaster and Caenorhabditis elegans belong to the coronin family of WD-repeat domain-containing proteins. Coronin7 proteins are characterized by two WD-repeat domains that presumably fold into two β-propeller structures. DdCRN7 shares highest homology with human CRN7, a protein with roles in membrane trafficking. DdCRN7 is present in the cytosol and accumulates in cell surface projections during movement and phago- and pinocytosis. Cells lacking CRN7 have altered chemotaxis and phagocytosis. Furthermore, loss of CRN7 affects the infection process by the pathogen Legionella pneumophila and allows a more efficient internalization of bacteria. To provide a mechanism for CNR7 action, we studied actin-related aspects. We could show that CRN7 binds directly to F-actin and protects actin filaments from depolymerization. CRN7 also associated with F-actin in vivo. It was present in the Triton X-100-insoluble cytoskeleton, colocalized with F-actin, and its distribution was sensitive to drugs affecting the actin cytoskeleton. We propose that the CRN7 role in chemotaxis and phagocytosis is through its effect on the actin cytoskeleton.