The scaffolding protein GRASP/Tamalin directly binds to Dock180 as well as to cytohesins facilitating GTPase crosstalk in epithelial cell migration

BMC Cell Biology

Lorraine C Santy¹  Myriam A Attar¹ 

[1] Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 208 Althouse Lab, University Park, PA 16802, USA

关键词: Arf6 and Rac1;    Dock180;    Tamalin;    GRASP;    Cytohesin;   

Others  :  855485
DOI  :  10.1186/1471-2121-14-9

 received in 2012-08-27, accepted in 2013-02-20,  发布年份 2013

【 摘 要 】

Background

The transition of epithelial cells from their normal non-motile state to a motile one requires the coordinated action of a number of small GTPases. We have previously shown that epithelial cell migration is stimulated by the coordinated activation of Arf and Rac GTPases. This crosstalk depends upon the assembly of a multi-protein complex that contains the Arf-activating protein cytohesin 2/ARNO and the Rac activating protein Dock180. Two scaffolding proteins that bind directly to cytohesin 2 organize this complex.

Results

We now have found that Rac activation in response to hepatocyte growth factor (HGF) requires cytohesin 2 and Dock180. GRASP/Tamalin is one of the scaffolds that builds the complex containing cytohesin 2 and Dock180. We determine here that the Ala/Pro rich region of GRASP directly interacts with the SH3 domain of Dock180. By binding to both cytohesin 2/ARNO and Dock180, GRASP bridges the guanine nucleotide exchange factors (GEFs) that activate Arf and Rac, thereby promoting Arf-to-Rac signaling. Furthermore, we find that knockdown of GRASP impairs hepatocyte growth factor (HGF)-stimulated Rac activation and HGF-stimulated epithelial migration.

Conclusions

GRASP binds directly both cytohesin 2 and Dock180 to coordinate their activities, and by doing so promotes crosstalk between Arf and Rac.

【 授权许可】

   
2013 Attar and Santy; licensee BioMed Central Ltd.

【 图 表 】

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