Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development

Am J Pathol. 2006 Dec;169(6):2209-22. doi: 10.2353/ajpath.2006.060562.


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-1alpha and -1beta cDNAs were functionally characterized in the zebrafish. Cav-1alpha and -1beta 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-1alpha/cav-1alpha) but not heterotypic (cav-1alpha/cav-1beta) 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-1alpha (Y14-->F) resulted in a failure to rescue the cav-1alpha morphant phenotype, verifying an essential role for Cav-1alpha specifically and implicating this residue in early developmental functions. Cav-1alpha and -1beta morphants also exhibited disruption in the actin cytoskeleton. These results support important and previously unanticipated roles for the Caveolin-1 isoforms in vertebrate organogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Caveolae / chemistry
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Caveolin 1 / physiology*
  • Cell Line
  • Humans
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Notochord / blood supply
  • Notochord / embryology
  • Phosphorylation
  • Protein Isoforms
  • RNA, Messenger
  • Sequence Homology, Amino Acid
  • Somites / metabolism
  • Tissue Distribution
  • Transfection
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / physiology*


  • Actins
  • Caveolin 1
  • Protein Isoforms
  • RNA, Messenger
  • Zebrafish Proteins

Associated data

  • GENBANK/AY124572
  • GENBANK/AY124573