Caveolin3

Caveolin-3 (Cav-3) is a protein belonging to the caveolin family and is encoded by the CAV3 gene in humans. It is a muscle-specific caveolin and serves as the principal caveolin protein in skeletal and cardiac muscle cells. Cav-3 localizes to caveolae, the cholesterol- and sphingolipid-rich invaginations of the plasma membrane, where it participates in the formation and stabilization of these membrane structures in muscle tissue.

In cells, Cav-3 acts as a scaffolding protein within caveolae, organizing and regulating signaling molecules such as kinases, ion channels, and G proteins. Through this role, it modulates pathways related to membrane integrity, mechanotransduction, and lipid homeostasis. Cav-3 also contributes to sarcolemmal stability during muscle contraction and to the proper trafficking of caveolar components.

Structurally, Cav-3 is an integral membrane protein with cytoplasmic N- and C- termini and a central hydrophobic domain that spans the plasma membrane. It contains a caveolin scaffolding domain that mediates interactions with signaling proteins, enabling selective regulation of signaling in muscle membranes.

Mutations in CAV3 give rise to a group of disorders known as caveolinopathies, which include limb-girdle muscular dystrophy type 1C (LGMD-1C) and rippling muscle disease. Other muscular phenotypes, such as distal myopathy and cardiomyopathy, have been reported. Inheritance is typically autosomal dominant with variable expressivity, though de novo mutations occur. Pathophysiology often involves disrupted caveolae formation or altered signaling, leading to membrane instability and abnormal signal transduction.

Diagnosis commonly involves genetic testing for CAV3 variants, supplemented by muscle biopsy showing reduced caveolin-3 staining or disorganized caveolae. Management is supportive, while research seeks therapies that address membrane integrity and caveolar signaling.