Three diagrams show disease conditions associated with CAV3 and CAVIN1, including rippling muscle disease, hyperCKemia, exercise intolerance, myalgia, rhabdomyolysis, muscular dystrophy, and cardiac dysfunction. It also compares Type I and Type II caveolinopathies based on caveola formation, CAV3 expression, and Cavin1 recruitment. A CAV3 membrane structure and domain map identify disease-associated variants and their locations.
Muscle disease conditions associated with dysfunction of caveolae. Left: Symptoms of caveola-associated muscle diseases and AlphaFold3 model of the CAV3 8S oligomer. Zoomed in area shows the position of the Pro residue at position 104 that is substituted by Leu in one of the best-studied caveolinopathies, CAV3-P104L. Right: proposed scheme for classification of caveolinopathies and associated variants. Representative type I and type II CAV3 variants and their associated clinical features (Betz et al., 2001; de Paula et al., 2001; Figarella-Branger et al., 2003; Herrmann et al., 2000; McNally et al., 1998; Minetti et al., 1998; Scalco et al., 2016; Traverso et al., 2008) are shown along with the CAV3 protein structure, which includes the following structural motifs (Porta et al., 2022): PIN motif (PIN), oligomerization domain (OD) containing the signature motif (SM) and scaffolding domain (SD), intramembrane domain (IMD), and spoke region (SR); N, N-terminus and C, C-terminus; DM, distal myopathy; HCK, HyperCKemia.