title: Endosomes generate localized Rho-ROCK-MLC2-based contractile signals via Endo180 to promote adhesion disassembly.
abstract: The regulated assembly and disassembly of focal adhesions and adherens junctions contributes to cell motility and tumor invasion. Pivotal in this process is phosphorylation of myosin light chain-2 (MLC2) by Rho kinase (ROCK) downstream of Rho activation, which generates the contractile force necessary to drive disassembly of epithelial cell-cell junctions and cell-matrix adhesions at the rear of migrating cells. How Rho-ROCK-MLC2 activation occurs at these distinct cellular locations is not known, but the emerging concept that endocytic dynamics can coordinate key intracellular signaling events provides vital clues. We report that endosomes containing the promigratory receptor Endo180 (CD280) can generate Rho-ROCK-MLC2-based contractile signals. Moreover, we provide evidence for a cellular mechanism in which Endo180-containing endosomes are spatially localized to facilitate their contractile signals directly at sites of adhesion turnover. We propose migration driven by Endo180 as a model for the spatial regulation of contractility and adhesion dynamics by endosomes.
authors.affiliation: Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, England, UK.
authors.forename: Justin
authors.initials: J
authors.lastname: Sturge
authors.forename: Dirk
authors.initials: D
authors.lastname: Wienke
authors.forename: Clare M
authors.initials: CM
authors.lastname: Isacke
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D024722:Cardiac Myosins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D011992:Endosomes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases
chemical_list: C408294:Endo180; D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D011990:Receptors, Transferrin; D055293:Receptors, Urokinase Plasminogen Activator; C107184:myosin light chain 2; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D024722:Cardiac Myosins; D020741:rho GTP-Binding Proteins