C‐terminus of caveolin‐1 plays a critical role in endothelial cell migration and cell metabolism

Caveolins are evolutionary conserved plasma membrane proteins necessary for the formation of caveolae in diverse cell types. Caveolae are involved in intracellular transport, extracellular secretion, cell signaling and cellular homeostasis. Caveolin‐1 (Cav‐1) mutations in the C‐terminus are associated with pulmonary hypertension, progeria like syndrome, and lipodystrophy. However, the mechanisms by which C‐terminal Cav‐1 mutations cause disease etiology is unclear. Pulmonary hypertension is characterized by endothelial cell dysfunction in pulmonary arteries. We hypothesized that Cav‐1 mutant protein (c.478_479delTT) alters endothelial cell metabolism and migration. Primary endothelial cells were treated with HIV1‐CMV‐GFP or HIV1‐CMV‐hCav1‐159 lentiviral vector representing the C‐terminus‐mutated Cav‐1 protein for 48hr followed by wound healing assay and mitochondrial structure and function assessed by electron microscopy and Seahorse extracellular flux assay, respectively. We also assessed for biochemical markers such as focal adhesion kinase protein expression (FAK) involved in cell migration. Cells treated with Cav‐1 mutant virus showed 60% inhibition of endothelial cell migration compared to GFP controls. Electron microscopy revealed small and rounded mitochondria with disorganized cristae in cells treated with Cav‐1 mutant. The maximal respiration was reduced in cells treated with Cav‐1 mutant. FAK expression was downregulated in cells treated with Cav‐1 mutant suggesting a FAK mediated inhibition of endothelial cell migration. Conclusions The C‐terminus of Cav‐1 may be an as of yet poorly understood but critical regulator of endothelial function and metabolism. Support or Funding Information NA