RIAM activates integrins by linking talin to ras GTPase membrane-targeting sequences.

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  • Author(s): Lee HS;Lee HS; Lim CJ; Puzon-McLaughlin W; Shattil SJ; Ginsberg MH
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2009 Feb 20; Vol. 284 (8), pp. 5119-27. Date of Electronic Publication: 2008 Dec 19.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Adaptor Proteins, Signal Transducing/*metabolism ; Carrier Proteins/*metabolism ; Cell Membrane/*metabolism ; Integrins/*metabolism ; Membrane Proteins/*metabolism ; Talin/*metabolism ; rap1 GTP-Binding Proteins/*metabolism; Adaptor Proteins, Signal Transducing/genetics ; Amino Acid Sequence/physiology ; Animals ; Binding Sites/physiology ; CHO Cells ; Carrier Proteins/genetics ; Cell Membrane/genetics ; Cricetinae ; Cricetulus ; Humans ; Integrins/genetics ; Membrane Proteins/genetics ; Protein Sorting Signals ; Protein Structure, Tertiary/physiology ; Protein Transport/physiology ; Proto-Oncogene Proteins p21(ras)/genetics ; Proto-Oncogene Proteins p21(ras)/metabolism ; Talin/genetics ; rap1 GTP-Binding Proteins/genetics
    • Abstract:
      Rap1 small GTPases interact with Rap1-GTP-interacting adaptor molecule (RIAM), a member of the MRL (Mig-10/RIAM/Lamellipodin) protein family, to promote talin-dependent integrin activation. Here, we show that MRL proteins function as scaffolds that connect the membrane targeting sequences in Ras GTPases to talin, thereby recruiting talin to the plasma membrane and activating integrins. The MRL proteins bound directly to talin via short, N-terminal sequences predicted to form amphipathic helices. RIAM-induced integrin activation required both its capacity to bind to Rap1 and to talin. Moreover, we constructed a minimized 50-residue Rap-RIAM module containing the talin binding site of RIAM joined to the membrane-targeting sequence of Rap1A. This minimized Rap-RIAM module was sufficient to target talin to the plasma membrane and to mediate integrin activation, even in the absence of Rap1 activity. We identified a short talin binding sequence in Lamellipodin (Lpd), another MRL protein; talin binding Lpd sequence joined to a Rap1 membrane-targeting sequence is sufficient to recruit talin and activate integrins. These data establish the mechanism whereby MRL proteins interact with both talin and Ras GTPases to activate integrins.
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    • Grant Information:
      AR27214 United States AR NIAMS NIH HHS; HL 078784 United States HL NHLBI NIH HHS; HL 31950 United States HL NHLBI NIH HHS; U54 GM06434 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (APBB1IP protein, human)
      0 (Adaptor Proteins, Signal Transducing)
      0 (Carrier Proteins)
      0 (Integrins)
      0 (Membrane Proteins)
      0 (Protein Sorting Signals)
      0 (RAP1A protein, human)
      0 (RAPH1 protein, human)
      0 (Talin)
      EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
      EC 3.6.5.2 (rap1 GTP-Binding Proteins)
    • Publication Date:
      Date Created: 20081223 Date Completed: 20090413 Latest Revision: 20211020
    • Publication Date:
      20240829
    • Accession Number:
      PMC2643525
    • Accession Number:
      10.1074/jbc.M807117200
    • Accession Number:
      19098287