title: Calcium and calmodulin-dependent serine/threonine protein kinase type II (CaMKII)-mediated intramolecular opening of integrin cytoplasmic domain-associated protein-1 (ICAP-1α) negatively regulates β1 integrins.
abstract: Focal adhesion turnover during cell migration is an integrated cyclic process requiring tight regulation of integrin function. Interaction of integrin with its ligand depends on its activation state, which is regulated by the direct recruitment of proteins onto the β integrin chain cytoplasmic domain. We previously reported that ICAP-1α, a specific cytoplasmic partner of β1A integrins, limits both talin and kindlin interaction with β1 integrin, thereby restraining focal adhesion assembly. Here we provide evidence that the calcium and calmodulin-dependent serine/threonine protein kinase type II (CaMKII) is an important regulator of ICAP-1α for controlling focal adhesion dynamics. CaMKII directly phosphorylates ICAP-1α and disrupts an intramolecular interaction between the N- and the C-terminal domains of ICAP-1α, unmasking the PTB domain, thereby permitting ICAP-1α binding onto the β1 integrin tail. ICAP-1α direct interaction with the β1 integrin tail and the modulation of β1 integrin affinity state are required for down-regulating focal adhesion assembly. Our results point to a molecular mechanism for the phosphorylation-dependent control of ICAP-1α function by CaMKII, allowing the dynamic control of β1 integrin activation and cell adhesion.
authors.affiliation: Institut Albert Bonniot U823, INSERM, F-38042 Grenoble, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Millon-Frémillon
authors.forename: Molly
authors.initials: M
authors.lastname: Brunner
authors.forename: Nadia
authors.initials: N
authors.lastname: Abed
authors.forename: Elodie
authors.initials: E
authors.lastname: Collomb
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Ribba
authors.forename: Marc R
authors.initials: MR
authors.lastname: Block
authors.forename: Corinne
authors.initials: C
authors.lastname: Albigès-Rizo
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouvard
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D016466:CHO Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D022001:Focal Adhesions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008954:Models, Biological; D009154:Mutation; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D013912:Threonine; C512603:ICAP-1 protein, mouse; C072105:KN 93; D000096926:Benzenesulfonamides
keywords: Adhesion; CaMKII; Focal Adhesion; ICAP-1; Integrins; Membrane Proteins; Signal Transduction