Caveolin-1α and −1β Perform Nonredundant Roles in Early Vertebrate Development

Caveolins are integral membrane proteins that localize predominantly to lipid rafts, where they oligomerize to form flask-shaped organelles termed caveolae and play important roles in membrane trafficking, signal transduction, and other cellular processes. To investigate potential roles for caveolin-1 (cav-1) in development, cav-1α and -1β cDNAs were functionally characterized in the zebrafish. Cav-1α and −1β mRNAs exhibited overlapping but distinct expression patterns throughout embryogenesis. Targeted depletion of either Cav-1 isoform, using antisense morpholino oligomers, resulted in a substantial loss of caveolae and dramatic neural, eye, and somite defects by 12 hours after fertilization, the time at which mRNA levels of both isoforms substantially increased in wild-type animals. Morphant phenotypes were rescued by injection of homotypic (cav-1α/cav-1α) but not heterotypic (cav-1α/cav-1β) zebrafish and human cav-1 cRNAs, revealing nonredundant and evolutionarily conserved functions for the individual Cav-1 isoforms. Mutation of a known Cav-1 phosphorylation site unique to Cav-1α (Y14→F) resulted in a failure to rescue the cav-1α morphant phenotype, verifying an essential role for Cav-1α specifically and implicating this residue in early developmental functions. Cav-1α and -1β morphants also exhibited disruption in the actin cytoskeleton. These results support important and previously unanticipated roles for the Caveolin-1 isoforms in vertebrate organogenesis.