A Role for Caveolin-3 in the Pathogenesis of Muscular Dystrophies

Abstract

Caveolae are the cholesterol-rich small invaginations of the plasma membrane present in many cell types including adipocytes, endothelial cells, epithelial cells, fibroblasts, smooth muscles, skeletal muscles and cardiac muscles. They serve as specialized platforms for many signaling molecules and regulate important cellular processes like energy metabolism, lipid metabolism, mitochondria homeostasis, and mechano-transduction. Caveolae can be internalized together with associated cargo. The caveolae-dependent endocytic pathway plays a role in the withdrawal of many plasma membrane components that can be sent for degradation or recycled back to the cell surface. Caveolae are formed by oligomerization of caveolin proteins. Caveolin-3 is a muscle-specific isoform, whose malfunction is associated with several diseases including diabetes, cancer, atherosclerosis, and cardiovascular diseases. Mutations in Caveolin-3 are known to cause muscular dystrophies that are collectively called caveolinopathies. Altered expression of Caveolin-3 is also observed in Duchenne’s muscular dystrophy, which is likely a part of the pathological process leading to muscle weakness. This review summarizes the major functions of Caveolin-3 in skeletal muscles and discusses its involvement in the pathology of muscular dystrophies.

The Dystrophin Node as Integrator of Cytoskeletal Organization, Lateral Force Transmission, Fiber Stability and Cellular Signaling in Skeletal Muscle

“…These structures are involved in lipid storage, endocytosis, cellular signaling and mechano-protection [ 116 ]. Freeze-fracture electron microscopy has established that the number and structure of caveolae are changed in dystrophinopathy, suggesting an important role of abnormal cavins in muscular dystrophy [ 39 , 117 ]. Of note, the crucial repair protein myoferlin [ 118 ] is also closely associated with caveolin and intrinsically involved in the maintenance and structural integrity of the sarcolemmal membrane, together with the Ca 2+ -dependent repair protein dysferlin [ 119 ].…”

“…Caveolinopathies are another group of disorders that affect the plasma membrane via alterations in caveolae invaginations. Primary abnormalities in caveolin-3 are associated with certain forms of muscular dystrophy and the altered expression of this protein is postulated to also play a pathophysiological role in dystrophinopathy [ 39 ]. Importantly, new findings on the underlying mechanisms of dystrophic alterations are crucial for the identification of robust and disease-specific biomarker molecules [ 40 , 41 , 42 , 43 ] and the development of novel diagnostic approaches [ 44 ], as well as the design of innovative therapies to restore the dystrophin complex and counteract secondary aspects involved in progressive muscle wasting [ 45 , 46 , 47 , 48 , 49 ].…”

SNTA1-deficient human cardiomyocytes are associated with increased structural components, calcium handling disorder, and shorter field potential duration

“…The CICR is a critical procedure of EC in ventricular myocytes. The second protein is caveolin 3 (CAV3), a member of caveolin protein family that contribute to the formation of caveolae and provide microdomains for a variety of functional proteins in T-tubules [30][31][32]. The third protein is bridging integrator 1 (BIN1), one of the membrane scaffolding proteins, which interact between BAR domain and phospholipid acid in the cell membrane to deform the membrane bilayer.…”

Extracellular Matrix and the Production of Cultured Meat

“…Dystrophin is a rod-shaped large protein (430-kDa) molecule. Dystrophin interacts with β-dystroglycan to stabilize dystroglycan and dystrophin glycoprotein complex [ 81 ]. The dystrophin glycoprotein complex connects the ECM to the actin cytoskeleton in striated muscle cells and mediates three key functions such as structural stability of plasma membrane, ion homeostasis, and transmembrane signaling [ 82 ].…”