Soleus muscle in glycosylation-deficient muscular dystrophy is protected from contraction-induced injury.
The glycosylation of dystroglycan is required for its function as a high-affinity laminin receptor, and loss of dystroglycan glycosylation results in congenital muscular dystrophy. The purpose of this study was to investigate the functional defects in slow- and fast-twitch muscles of glycosylation-deficient Large(myd) mice. While a partial alteration in glycosylation of dystroglycan in heterozygous Large(myd/+) mice was not sufficient to alter muscle function, homozygous Large(myd/myd) mice demonstrated a marked reduction in specific force in both soleus and extensor digitorum longus (EDL) muscles. Although EDL muscles from Large(myd/myd) mice were highly susceptible to lengthening contraction-induced injury, Large(myd/myd) soleus muscles surprisingly showed no greater force deficit compared with wild-type soleus muscles even after five lengthening contractions. Despite no increased susceptibility to injury, Large(myd/myd) soleus muscles showed loss of dystroglycan glycosylation and laminin binding activity and dystrophic pathology. Interestingly, we show that soleus muscles have a markedly higher sarcolemma expression of β(1)-containing integrins compared with EDL and gastrocnemius muscles. Therefore, we conclude that β(1)-containing integrins play an important role as matrix receptors in protecting muscles containing slow-twitch fibers from contraction-induced injury in the absence of dystroglycan function, and that contraction-induced injury appears to be a separable phenotype from the dystrophic pathology of muscular dystrophy.
Gumerson
Jessica D
JD
Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-0622, USA.
Kabaeva
Zhyldyz T
ZT
Davis
Carol S
CS
Faulkner
John A
JA
Michele
Daniel E
DE
D000818:Animals; D049030:Dystroglycans / Q000378:metabolism*; D006031:Glycosylation; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism / Q000473:pathology
D019012:Integrin beta1; D007797:Laminin; D049030:Dystroglycans