Caveolin-1α and -1β perform nonredundant roles in early vertebrate development

Abstract

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 wildtype 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. Copyright © American Society for Investigative Pathology.