RIAM是一种Ena/VASP和丝切蛋白配体，它与Rap1-GTP相互作用并介导Rap1诱导的黏附。

RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion.

作者信息

Lafuente Esther M, van Puijenbroek André A F L, Krause Matthias, Carman Christopher V, Freeman Gordon J, Berezovskaya Alla, Constantine Erica, Springer Timothy A, Gertler Frank B, Boussiotis Vassiliki A

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Dev Cell. 2004 Oct;7(4):585-95. doi: 10.1016/j.devcel.2004.07.021.

DOI:10.1016/j.devcel.2004.07.021

PMID:15469846

Abstract

The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM also interacts with Profilin and Ena/VASP proteins, molecules that regulate actin dynamics. Overexpression of RIAM induced cell spreading and lamellipodia formation, changes that require actin polymerization. In contrast, RIAM knockdown cells had reduced content of polymerized actin. RIAM overexpression also induced integrin activation and cell adhesion. RIAM knockdown displaced Rap1-GTP from the plasma membrane and abrogated Rap1-induced adhesion. Thus, RIAM links Rap1 to integrin activation and plays a role in regulating actin dynamics.

摘要

小GTP酶Rap1可诱导整合素介导的黏附以及肌动蛋白细胞骨架的变化。介导Rap1这些作用的机制目前尚不清楚。我们已确定RIAM是一种与Rap1-GTP相互作用的衔接分子。RIAM定义了一类衔接分子家族，其包含一个RA样（Ras关联）结构域、一个PH（普列克底物蛋白同源）结构域以及各种富含脯氨酸的基序。RIAM还与抑制蛋白以及Ena/VASP蛋白相互作用，这些蛋白是调节肌动蛋白动力学的分子。RIAM的过表达诱导了细胞铺展和片状伪足形成，这些变化需要肌动蛋白聚合。相反，RIAM基因敲低的细胞中聚合肌动蛋白的含量减少。RIAM的过表达还诱导了整合素激活和细胞黏附。RIAM基因敲低使Rap1-GTP从质膜上移位，并消除了Rap1诱导的黏附。因此，RIAM将Rap1与整合素激活联系起来，并在调节肌动蛋白动力学中发挥作用。