Impact of novel Caveolin-1 frameshift mutants on caveolae assembly and function

Abstract

Caveolin-1 (CAV1) is an essential protein for the formation of caveolae, invaginations found at the plasma membrane. Caveolae are abundant in many cell types and numerous functions have been identified, including modulating cell signaling and buffering cells from mechanical stress. However, exactly how newly identified mutant forms of CAV1 impact caveolae formation and function remains to be elucidated. Previous work has highlighted the importance of the C-terminus of CAV1 in the assembly of CAV1 complexes, and trafficking to the plasma membrane. Investigation of the frameshift mutant CAV1-P158 and the truncation mutant CAV1-F160X revealed that alteration of the amino acid sequence, or truncation of the C-terminus of CAV1 had little effect on caveolae assembly. Interestingly, incorporation of these mutant proteins into hybrid caveolae with wild type CAV1 led to the formation of caveolae with altered biochemical and molecular properties, indicating that an intact C-terminus may also be important for normal caveolae function. Thus, the incorporation of CAV1 proteins with C-terminal mutations into caveolae is a critical factor associated with human diseases.