title: Cib2 binds integrin alpha7Bbeta1D and is reduced in laminin alpha2 chain-deficient muscular dystrophy.
abstract: Mutations in the gene encoding laminin alpha2 chain cause congenital muscular dystrophy type 1A. In skeletal muscle, laminin alpha2 chain binds at least two receptor complexes: the dystrophin-glycoprotein complex and integrin alpha7beta1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin alpha2 chain-deficient mouse limb muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium- and integrin-binding protein 2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin alphaIIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin alpha7beta1-binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle, Cib2 colocalizes with the integrin alpha7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium-binding protein that interacts with integrin alpha7Bbeta1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin alpha7Bbeta1D signaling in skeletal muscle.
authors.affiliation: Department of Experimental Medical Science, Division for Cell and Matrix Biology, University of Lund, 221 84 Lund, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Häger
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Bigotti
authors.forename: Renata
authors.initials: R
authors.lastname: Meszaros
authors.forename: Virginie
authors.initials: V
authors.lastname: Carmignac
authors.forename: Johan
authors.initials: J
authors.lastname: Holmberg
authors.forename: Valérie
authors.initials: V
authors.lastname: Allamand
authors.forename: Mikael
authors.initials: M
authors.lastname: Akerlund
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kalamajski
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancaccio
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mayer
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durbeej
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000196:embryology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D040201:Platelet Membrane Glycoprotein IIb / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D012508:Sarcolemma / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; C491605:Cib1 protein, mouse; C532307:Cib2 protein, mouse; D016023:Integrins; D007797:Laminin; D040201:Platelet Membrane Glycoprotein IIb; C102645:laminin alpha 2; C082908:integrin alpha7beta1