Tropomyosin Tm5NM1 Spatially Restricts Src Kinase Activity through Perturbation of Rab11 Vesicle Trafficking |
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| Authors: | Cuc T Bach Rachael Z Murray Dylan Owen Kat Gaus Geraldine M O'Neill |
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| Institution: | aChildren''s Cancer Research Unit, Kids Research Institute, The Children''s Hospital at Westmead, Sydney, Australia;bDiscipline of Paediatrics and Child Health, The University of Sydney, Sydney, Australia;cInstitute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia;dCentre for Vascular Research and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia |
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| 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. |
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