PUBLICATION
Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development
- Authors
- Fang, P.K., Solomon, K.R., Zhuang, L., Qi, M., McKee, M., Freeman, M.R., and Yelick, P.C.
- ID
- ZDB-PUB-061227-25
- Date
- 2006
- Source
- The American journal of pathology 169(6): 2209-2222 (Journal)
- Registered Authors
- Fang, Pingke, Yelick, Pamela C.
- Keywords
- none
- 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*
- PubMed
- 17148682 Full text @ Am. J. Pathol.
Citation
Fang, P.K., Solomon, K.R., Zhuang, L., Qi, M., McKee, M., Freeman, M.R., and Yelick, P.C. (2006) Caveolin-1alpha and -1beta perform nonredundant roles in early vertebrate development. The American journal of pathology. 169(6):2209-2222.
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-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping