Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation

Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation
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DOI:
10.1182/blood.v98.4.1142
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发表时间:
2001-08-15
期刊:
影响因子:
20.3
通讯作者:
Jones, GE
Jones, GE
中科院分区:
医学1区
文献类型:
--
作者:
Burns, S;Thrasher, AJ;Jones, GE

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树突状细胞(dc)迁移过程中配置细胞骨架的细胞机制尚不清楚。未成熟的dc在其前缘组装称为足质体的专门粘附结构;这些与Wiskott-Aldrich综合征蛋白(WASp)和组织肌动蛋白相关蛋白2/3复合物的肌动蛋白的局部募集有关。在缺乏WASp的未成熟dc中,足体缺失,残余的畸形板足和丝状足不极化,迁移严重受损。显微注射研究表明,足小体的组装和极化需要Cdc42、Rac和Rho的协同作用,从而提供了序列突出和粘附活性之间的联系。足小体的形成仅限于具有不成熟表型的细胞,这表明这些结构在早期迁移阶段具有特定作用。
The cellular mechanisms that configure the cytoskeleton during migration of dendritic cells (DCs) are poorly understood. Immature DCs assemble specialized adhesion structures known as podosomes at their leading edge; these are associated with the localized recruitment of the Wiskott-Aldrich Syndrome protein (WASp) and the actin organizing actin-related protein 2/3 complex. In immature DCs lacking WASp, podosomes are absent, residual dysmorphic lamellipodia and filopodia are nonpolarized, and migration is severely compromised. Microinjection studies indicate that podosome assembly and polarization require concerted action of Cdc42, Rac, and Rho, thereby providing a link between sequential protrusive and adhesive activity. Formation of podosomes is restricted to cells with an immature phenotype, indicating a specific role for these structures during the early migratory phase.