title: Reggie-1/Flotillin-2 regulates integrin trafficking and focal adhesion turnover via Rab11a.
abstract: Reggies/flotillins are implicated in trafficking of membrane proteins to their target sites and in the regulation of the Rab11a-dependent targeted recycling of E-cadherin to adherens junctions (AJs). Here we demonstrate a function of reggies in focal adhesion (FA) formation and α5- and β1-integrin recycling to FAs. Downregulation of reggie-1 in HeLa and A431 cells by siRNA and shRNA increased the number of FAs, impaired their distribution and modified FA turnover. This was coupled to enhanced focal adhesion kinase (FAK) and Rac1 signaling and gain in plasma membrane motility. Wild type and constitutively-active (CA) Rab11a rescued the phenotype (normal number of FAs) whereas dominant-negative (DN) Rab11a mimicked the loss-of-reggie phenotype in control cells. That reggie-1 affects integrin trafficking emerged from the faster loss of internalized antibody-labeled β1-integrin in reggie-deficient cells. Moreover, live imaging using TIRF microscopy revealed vesicles containing reggie-1 and α5- or β1-integrin, trafficking close to the substrate-near membrane and making kiss-and-run contacts with FAs. Thus, reggie-1 in interaction with Rab11a controls Rac1 and FAK activation and coordinates the targeted recycling of α5- and β1-integrins to FAs to regulate FA formation and membrane dynamics.
authors: Department of Biology, University of Konstanz, 78467 Konstanz, Germany. Electronic address: Nikola.Huelsbusch@uni-Konstanz.de.
authors: Nikola
authors: N
authors: Hülsbusch
authors: Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Gonzalo P
authors: GP
authors: Solis
authors: Department of Pharmacology and Toxicology, University of Lausanne, CH-1005 Lausanne, Switzerland.
authors: Vladimir L
authors: VL
authors: Katanaev
authors: Department of Biology, University of Konstanz, 78467 Konstanz, Germany. Electronic address: Claudia.Stuermer@uni-Konstanz.de.
authors: Claudia A O
authors: CA
authors: Stuermer
mesh_terms: D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D051416:Focal Adhesion Protein-Tyrosine Kinases; D039482:Integrin alpha5; D019012:Integrin beta1; D008565:Membrane Proteins; D020691:rab GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000099193:rab11 GTP-Binding Proteins; C107953:RAC1 protein, human; C106354:flotillins
keywords: Cargo trafficking; Focal adhesion; Integrin; Rab11; Reggie/flotillin; Targeted delivery