The Caveolin3 complex stabilizes functional surface expression of the Lactate-Proton Shuttle McT1 but not the sodium channel Nav1.5 in cardiomyocytes

Caveolin3 variants were associated with action potential prolongation. As Caveolin1 was recently identified in cardiomyocytes, we hypothesize that conserved isoform-specific protein interactions underlie human loss-of-function variants. To analyze the Caveolin1 and Caveolin3 interactome, we developed unbiased live-cell proteomic and isoform-specific mass spectrometry techniques. We demonstrate the functional relevance and pathogenic mechanism of a novel Caveolin3 interactor in gene-edited human iPSC-cardiomyocyte models.