Muscle fibers attach to laminin in the basal lamina using two distinct mechanisms: dystrophin glycoprotein complex and α7β1 integrin. Defects these linkage systems result Duchenne muscular dystrophy (DMD), α2 congenital dystrophy, sarcoglycan-related α7 integrin dystrophy. Therefore, molecular continuity between extracellular matrix cell cytoskeleton is essential for structural functional integrity of skeletal muscle. To test whether can compensate absence dystrophin, we expressed rat chain...

The dystrophin glycoprotein complex links laminin in the extracellular matrix to cell cytoskeleton. Loss of causes Duchenne muscular dystrophy, most common human X-chromosome-linked genetic disease. α7β1 integrin is a second transmembrane receptor expressed skeletal muscle. Mutations α7 gene cause congenital myopathy humans and mice. increased muscle dystrophy patients mdx This observation has led suggestion that have complementary functional structural roles. To test this hypothesis, we...

Alpha7beta1-integrin links laminin in the extracellular matrix with cell cytoskeleton and therein mediates transduction of mechanical forces into chemical signals. Muscle contraction stretching ex vivo result activation intracellular signaling molecules that are integral to postexercise injury responses. Because alpha7beta1-integrin stabilizes muscle provides communication between cytoskeleton, role this integrin exercise-induced skeletal damage was assessed wild-type transgenic mice...

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin results reduced sarcolemmal integrity and increased susceptibility to muscle damage. The alpha(7)beta(1)-integrin laminin-binding protein up-regulated skeletal DMD patients mdx mouse model. Transgenic overexpression alpha(7)-integrin alleviates dystrophic mice, making this target for pharmacological intervention. Studies suggest laminin may regulate...

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a lethal muscle-wasting disease that caused by mutations in the LAMA2 gene, resulting loss of laminin-α2 protein. MDC1A patients exhibit severe muscle weakness from birth, are confined to wheelchair, require ventilator assistance, and have reduced life expectancy. There currently no effective treatments or cures for MDC1A. Laminin-α2 required formation heterotrimeric laminin-211 (ie, α2, β1, γ1) laminin-221 β2, γ1), which...

Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating neuromuscular disease caused by mutations in the LAMA2 gene. These result complete absence or truncated expression of laminin-α2 chain. The α2-chain major component laminin-211 and laminin-221 isoforms, predominant laminin isoforms healthy adult skeletal muscle. Mutations this chain progressive muscle degeneration as early neonatally. Laminin-211/221 ligand for cell receptors integrin-α7β1 α-dystroglycan. are...

We aimed to determine the frequency of all known forms congenital muscular dystrophy (CMD) in a large Australasian cohort.We screened 101 patients with CMD combination immunofluorescence, Western blotting, and DNA sequencing identify disease-associated abnormalities glycosylated alpha-dystroglycan, collagen VI, laminin alpha2, alpha7-integrin, selenoprotein.A total 45% cohort were assigned an immunofluorescent subgroup based on their abnormal staining pattern. Abnormal for alpha-dystroglycan...

The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in extracellular matrix with actin cytoskeleton. Several human muscular dystrophies arise from defects components this complex. alpha(7)beta(1)-integrin also binds and links Enhancement alpha(7)-integrin levels alleviates pathology mdx/utrn(-/-) mice, a model Duchenne dystrophy, thus integrin may functionally compensate for absence dystrophin. To test whether increasing affects transcription...

Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a severe and fatal muscle-wasting disease with no cure. MDC1A patients the dyW−/− mouse model exhibit muscle weakness, demyelinating neuropathy, failed regeneration premature death. We have recently shown that laminin-111, form of laminin found in embryonic skeletal muscle, can substitute for loss laminin-211/221 prevent progression model. What unclear from these studies whether laminin-111 restore to laminin-α2-deficient...

Abstract Background All types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant activation somatically silent DUX4 gene, expression which initiates a cascade cellular events ultimately leading to FSHD pathophysiology. Typically, progressive skeletal muscle weakness becomes noticeable in second or third decade life, yet there many individuals who genetically but develop symptoms much later life remain relatively asymptomatic throughout their lives. Conversely, may...

ABSTRACT The clustering of acetylcholine receptors (AChRs) in the post-synaptic membrane skeletal muscle is an early developmental event formation neuromuscular junction. Several studies show that laminin, as well neural agrin, can induce AChR C2C12 myofibers. We recently showed specific isoforms α7β1 integrin (a receptor normally found at junctions) colocalize and physically interact with clusters a laminin-dependent fashion. In contrast, induction agrin alone fails to promote localization...

The clustering of acetylcholine receptors (AChR) on skeletal muscle fibers is an early event in the formation neuromuscular junctions. Recent studies show that laminin as well agrin can induce AChR clustering. Since α7β1 integrin a major receptor muscle, we determined if this participates and/or agrin-induced alternative cytoplasmic domain variants, α7A and α7B, extracellular spliced forms, α7X1 α7X2, were studied for their ability to engage Immunofluorescence microscopy C2C12 myofibers...

Abstract The α7β1 integrin is a laminin receptor that has been implicated in muscle disease and the development of neuromuscular myotendinous junctions. Studies have shown also expressed nonskeletal tissues. To identify expression pattern α7 these tissues during embryonic development, chain knockout mice were generated by LacZ knockin strategy. In mice, from promoter reported β‐galactosidase. From day (ED) 11.5 to ED14.5, β‐galactosidase was detected developing central peripheral nervous...

Sarcospan (SSPN) is a core component of the major adhesion complexes in skeletal muscle, dystrophin– and utrophin (Utr)–glycoprotein (DGC UGC). We performed rigorous analysis SSPN-null mice discovered that loss SSPN decreased DGC UGC abundance, leading to impaired laminin-binding activity susceptibility eccentric contraction-induced injury muscle. show increased levels α7β1 integrin. To genetically test whether integrin compensates for function SSPN-nulls, we generated lacking both α7 (DKO,...

Dilated cardiomyopathy (DCM) is a disease of multifactorial etiologies, the risk which increased by male sex and age. There are few therapeutic options for patients with DCM who would benefit from identification common targetable pathways. We used bioinformatics to identify Nmrk2 gene involved in nicotinamide adenine dinucleotde (NAD) coenzyme biosynthesis as activated different mouse models hearts human while Nampt controlling parallel pathway repressed. A short NMRK2 protein isoform also...

The α7β1 integrin is increased in skeletal muscle response to injury-producing exercise, and transgenic overexpression of this mice protects against exercise-induced damage. present study investigates whether the increase observed wild-type exercise due transcriptional regulation examines mobilization at myotendinous junction (MTJ) a key determinant its protection A single bout downhill running selectively transcription α7 gene 5-wk-old 3 h postexercise, an chain was detected sarcolemma...

Merosin-deficient congenital muscular dystrophy 1A (MDC1A) is a devastating neuromuscular disease that results in children being confined to wheelchair, requiring ventilator assistance breathe and premature death. MDC1A caused by mutations the LAMA2 gene, which partial or complete loss of laminin-211 laminin-221, major laminin isoforms found basal lamina skeletal muscle. patients exhibit reduced α7β1 integrin; however, it unclear how secondary integrin contributes progression. To investigate...