RGD Reference Report - Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis. - Rat Genome Database

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Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis.

Authors: Volonte, D  McTiernan, CF  Drab, M  Kasper, M  Galbiati, F 
Citation: Volonte D, etal., Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H392-401. Epub 2007 Nov 2.
RGD ID: 8554071
Pubmed: PMID:17982011   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.01039.2007   (Journal Full-text)

Caveolae are 50- to 100-nm invaginations of the plasma membrane. Caveolins are the structural protein components of caveolar membranes. The caveolin gene family is composed of three members: caveolin-1, caveolin-2, and caveolin-3. Caveolin-1 and caveolin-2 are coexpressed in many cell types, including adipocytes, endothelial cells, epithelial cells, and fibroblasts. In contrast, caveolin-3 expression is essentially restricted to skeletal and smooth muscle cells as well as cardiac myocytes. While the interaction between caveolin-1 and caveolin-2 has been documented previously, the reciprocal interaction between endogenous caveolin-1 and caveolin-3 and their functional role in cell types expressing both isoforms have yet to be identified. Here we demonstrate for the first time that caveolin-1 and caveolin-3 are coexpressed in mouse and rat cardiac myocytes of the atria but not ventricles. We also found that caveolin-1 and caveolin-3 can interact and form heterooligomeric complexes in this cell type. Doxorubicin is an effective anticancer agent, but its use is limited by the possible development of cardiotoxicity. Using caveolin-1- and caveolin-3-null mice, we show that both caveolin-1 and caveolin-3 expression are required for doxorubicin-induced apoptosis in the atria through activation of caspase 3. Together, these results bring new insight into the functional role of caveolae and suggest that caveolin-1/caveolin-3 heterooligomeric complexes may play a key role in chemotherapy-induced cardiotoxicity in the atria.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cav3Ratcaveola located_inIDA PMID:17982011MGI 
Flot1Ratcaveola located_inIDA PMID:17982011MGI 

Objects Annotated

Genes (Rattus norvegicus)
Cav3  (caveolin 3)
Flot1  (flotillin 1)


Additional Information