Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7beta1 and dystroglycan.
Transgenically introduced laminin (LN) alpha1 chain prevents muscular dystrophy in LNalpha2 chain deficient mice. We now report increased integrin alpha7Bbeta1D synthesis in dystrophic LNalpha2 chain deficient muscle. Yet, immunofluorescence demonstrated a reduced expression of integrin alpha7B subunit at the sarcolemma. Transgenic expression of LNalpha1 chain reconstituted integrin alpha7B at the sarcolemma. Expression of alpha- and beta-dystroglycan is enhanced in LNalpha2 chain deficient muscle and normalized by transgenic expression of LNalpha1 chain. We suggest that LNalpha1 chain in part ameliorates the development of LNalpha2 chain deficient muscular dystrophy by retaining the binding sites for integrin alpha7Bbeta1D and alpha-dystroglycan, respectively.
Gawlik
Kinga I
KI
Department of Experimental Medical Science, Division for Cell and Matrix Biology, University of Lund, BMC B12 221 84 Lund, Sweden.
Mayer
Ulrike
U
Blomberg
Kristina
K
Sonnenberg
Arnoud
A
Ekblom
Peter
P
Durbeej
Madeleine
M
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D049030:Dystroglycans / Q000502:physiology*; D039001:Integrin alpha Chains / Q000378:metabolism; D016023:Integrins / Q000096:biosynthesis / Q000502:physiology*; D007797:Laminin / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000209:etiology / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism
D015703:Antigens, CD; D039001:Integrin alpha Chains; D016023:Integrins; D007797:Laminin; C085725:integrin alpha7; C102645:laminin alpha 2; D049030:Dystroglycans; C084098:laminin A; C082908:integrin alpha7beta1