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Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration.
García-Melero, Ana; Reverter, Meritxell; Hoque, Monira; Meneses-Salas, Elsa; Koese, Meryem; Conway, James R W; Johnsen, Camilla H; Alvarez-Guaita, Anna; Morales-Paytuvi, Frederic; Elmaghrabi, Yasmin A; Pol, Albert; Tebar, Francesc; Murray, Rachael Z; Timpson, Paul; Enrich, Carlos; Grewal, Thomas; Rentero, Carles.
Affiliation
  • García-Melero A; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Reverter M; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Hoque M; Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Meneses-Salas E; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Koese M; Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Conway JR; Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Johnsen CH; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Alvarez-Guaita A; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Morales-Paytuvi F; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain.
  • Elmaghrabi YA; Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia.
  • Pol A; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain, and.
  • Tebar F; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain, and.
  • Murray RZ; Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4095, Australia.
  • Timpson P; Garvan Institute of Medical Research and Kinghorn Cancer Centre, Cancer Research Program, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia.
  • Enrich C; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain, and enrich@ub.edu.
  • Grewal T; Faculty of Pharmacy, University of Sydney, Sydney, New South Wales 2006, Australia, thomas.grewal@sydney.edu.au.
  • Rentero C; From the Departament de Biologia Cel·lular, Immunologia i Neurociències, Facultat de Medicina, Universitat de Barcelona, 08036 Barcelona, Spain, Centre de Recerca Biomèdica CELLEX, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain, and carles.rentero@ub.edu.
J Biol Chem ; 291(3): 1320-35, 2016 Jan 15.
Article in En | MEDLINE | ID: mdl-26578516
Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and three-dimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of αVß3 and α5ß1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endosomes / Cholesterol / Annexin A6 / Integrin alpha5beta1 / Integrin alphaVbeta3 / Qa-SNARE Proteins Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: J Biol Chem Year: 2016 Document type: Article Affiliation country: España Country of publication: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Endosomes / Cholesterol / Annexin A6 / Integrin alpha5beta1 / Integrin alphaVbeta3 / Qa-SNARE Proteins Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: J Biol Chem Year: 2016 Document type: Article Affiliation country: España Country of publication: Estados Unidos