title: A RIAM/lamellipodin-talin-integrin complex forms the tip of sticky fingers that guide cell migration.
abstract: The leading edge of migrating cells contains rapidly translocating activated integrins associated with growing actin filaments that form 'sticky fingers' to sense extracellular matrix and guide cell migration. Here we utilized indirect bimolecular fluorescence complementation to visualize a molecular complex containing a Mig-10/RIAM/lamellipodin (MRL) protein (Rap1-GTP-interacting adaptor molecule (RIAM) or lamellipodin), talin and activated integrins in living cells. This complex localizes at the tips of growing actin filaments in lamellipodial and filopodial protrusions, thus corresponding to the tips of the 'sticky fingers.' Formation of the complex requires talin to form a bridge between the MRL protein and the integrins. Moreover, disruption of the MRL protein-integrin-talin (MIT) complex markedly impairs cell protrusion. These data reveal the molecular basis of the formation of 'sticky fingers' at the leading edge of migrating cells and show that an MIT complex drives these protrusions.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lagarrigue
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Praju
authors.initials: P
authors.lastname: Vikas Anekal
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Ho-Sup
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Alexia I
authors.initials: AI
authors.lastname: Bachir
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Jailal N
authors.initials: JN
authors.lastname: Ablack
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Horwitz
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Mark H
authors.identifier: http://orcid.org/0000-0002-5685-5417
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002477:Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D016608:Talin / Q000235:genetics / Q000378:metabolism*
chemical_list: C493340:APBB1IP protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D016023:Integrins; D008565:Membrane Proteins; C493339:RAPH1 protein, human; D016608:Talin