Myosin 2 is a key Rho kinase target necessary for the local concentration of E-cadherin at cell-cell contacts.
Classical cadherins accumulate at cell-cell contacts as a characteristic response to productive adhesive ligation. Such local accumulation of cadherins is a developmentally regulated process that supports cell adhesiveness and cell-cell cohesion. Yet the molecular effectors responsible for cadherin accumulation remain incompletely understood. We now report that Myosin 2 is critical for cells to concentrate E-cadherin at cell-cell contacts. Myosin 2 is found at cadherin-based cell-cell contacts and its recruitment requires E-cadherin activity. Indeed, both Myosin 2 recruitment and its activation were stimulated by E-cadherin homophilic ligation alone. Inhibition of Myosin 2 activity by blebbistatin or ML-7 rapidly impaired the ability of cells to concentrate E-cadherin at adhesive contacts, accompanied by decreased cadherin-based cell adhesiveness. The total surface expression of cadherins was unaffected, suggesting that Myosin 2 principally regulates the regional distribution of cadherins at the cell surface. The recruitment of Myosin 2 to cadherin contacts, and its activation, required Rho kinase; furthermore, inhibition of Rho kinase signaling effectively phenocopied the effects of Myosin 2 inhibition. We propose that Myosin 2 is a key effector of Rho-Rho kinase signaling that regulates cell-cell adhesion by determining the ability of cells to concentrate cadherins at contacts in response to homophilic ligation.
Shewan
Annette M
AM
Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Australia.
Maddugoda
Madhavi
M
Kraemer
Astrid
A
Stehbens
Samantha J
SJ
Verma
Suzie
S
Kovacs
Eva M
EM
Yap
Alpha S
AS
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D015820:Cadherins / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D001381:Azepines; D015820:Cadherins; D006576:Heterocyclic Compounds, 4 or More Rings; D009281:Naphthalenes; C070571:ML 7; C472645:blebbistatin; D024462:Myosin Type II; D024507:Nonmuscle Myosin Type IIA; D020741:rho GTP-Binding Proteins