title: MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly.
abstract: Although much is known about how individual cytoskeletal systems contribute to physiological processes such as cell migration and branching morphogenesis, little is known about how these different systems actively coordinate their functions after polymerization. Here we show that both fibroblasts and developing glands reciprocally coordinate levels of cellular contractility and microtubule acetylation. We find that this balance is achieved by interaction of the myosin phosphatase target subunit of myosin phosphatase with either myosin light chain or HDAC6, a microtubule deacetylase. This balance of contractility and microtubule acetylation controls progression of adhesion maturation by regulating surface density of α5β1 integrin and fibronectin. Thus, we propose that a homeostatic balance between contractility and microtubule acetylation is mediated by myosin phosphatase via controlled activation and deactivation of myosin II and HDAC6. This regulates the surface density of α5β1 integrin to modulate fibronectin matrix assembly and governs rates of cell migration and branching morphogenesis.
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: E Emily
authors.initials: EE
authors.lastname: Joo
authors.affiliation: Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
mesh_terms: D000107:Acetylation; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D021982:Cell-Matrix Junctions / Q000378:metabolism*; D003599:Cytoskeleton; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D013363:Submandibular Gland
chemical_list: D015820:Cadherins; C067625:FN1 protein, human; D005353:Fibronectins; D039081:Integrin alpha5beta1; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; C525088:Myh9 protein, mouse; D018994:Myosin Light Chains; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains