GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180

David T. White, Katie M. McShea, Myriam A. Attar, Lorraine C. Santy

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

ARFs are small GTPases that regulate vesicular trafficking, cell shape, and movement. ARFs are subject to extensive regulation by a large number of accessory proteins. The many different accessory proteins are likely specialized to regulate ARF signaling during particular processes. ARNO/cytohesin 2 is an ARF-activating protein that promotes cell migration and cell shape changes. We report here that protein - protein interactions mediated by the coiled-coil domain of ARNO are required for ARNO induced motility. ARNO lacking the coiled-coil domain does not promote migration and does not induce ARF-dependent Rac activation. We find that the coiled-coil domain promotes the assembly of a multiprotein complex containing both ARNO and the Rac-activating protein Dock180. Knockdown of either GRASP/Tamalin or IPCEF, two proteins known to bind to the coiled-coil of ARNO, prevents the association of ARNO and Dock180 and prevents ARNO-induced Rac activation. These data suggest that scaffold proteins can regulate ARF dependent processes by biasing ARF signaling toward particular outputs.

Original languageEnglish (US)
Pages (from-to)562-571
Number of pages10
JournalMolecular biology of the cell
Volume21
Issue number4
DOIs
StatePublished - Feb 15 2010

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Cell Movement
Proteins
Cell Shape
rac GTP-Binding Proteins
Multiprotein Complexes
Monomeric GTP-Binding Proteins
cytohesin-2

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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title = "GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180",
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GRASP and IPCEF promote ARF-to-Rac signaling and cell migration by coordinating the association of ARNO/cytohesin 2 with Dock180. / White, David T.; McShea, Katie M.; Attar, Myriam A.; Santy, Lorraine C.

In: Molecular biology of the cell, Vol. 21, No. 4, 15.02.2010, p. 562-571.

Research output: Contribution to journalArticle

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