title: Tropomyosin Tm5NM1 spatially restricts src kinase activity through perturbation of Rab11 vesicle trafficking.
abstract: In order for cells to stop moving, they must synchronously stabilize actin filaments and their associated focal adhesions. How these two structures are coordinated in time and space is not known. We show here that the actin association protein Tm5NM1, which induces stable actin filaments, concurrently suppresses the trafficking of focal-adhesion-regulatory molecules. Using combinations of fluorescent biosensors and fluorescence recovery after photobleaching (FRAP), we demonstrate that Tm5NM1 reduces the level of delivery of Src kinase to focal adhesions, resulting in reduced phosphorylation of adhesion-resident Src substrates. Live imaging of Rab11-positive recycling endosomes that carry Src to focal adhesions reveals disruption of this pathway. We propose that tropomyosin synchronizes adhesion dynamics with the cytoskeleton by regulating actin-dependent trafficking of essential focal-adhesion molecules.
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Sydney, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, Australia.
authors.forename: Cuc T
authors.initials: CT
authors.lastname: Bach
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Rachael Z
authors.initials: RZ
authors.lastname: Murray
authors.affiliation: Centre for Vascular Research and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia.
authors.forename: Dylan
authors.initials: D
authors.lastname: Owen
authors.affiliation: Centre for Vascular Research and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia.
authors.forename: Kat
authors.initials: K
authors.lastname: Gaus
authors.affiliation: Children's Cancer Research Unit, Kids Research Institute, The Children's Hospital at Westmead, Sydney, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, Australia geraldine.oneill@health.nsw.gov.au.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Neill
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000502:physiology*; D022001:Focal Adhesions / Q000502:physiology; D051379:Mice; D010766:Phosphorylation; D051381:Rats; D014335:Tropomyosin / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000502:physiology*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D014335:Tropomyosin; D020691:rab GTP-Binding Proteins; D019061:src-Family Kinases; D000099193:rab11 GTP-Binding Proteins