title: Cavin 1 function does not follow caveolar morphology.
abstract: The function of caveolae, small invaginations of the plasma membrane, remains a matter of debate. We discuss endocytosis and compartmentalization of metabolic and signaling pathways. Caveolin 3 (CAV3) and polymerase I and transcript release factor (PTRF) are important proteins that ensure shaping of caveolae in muscle cells. We investigated caveolae morphologically by electron microscopy in myotubes obtained from patients with CAV3 mutations and performed functional analyses in fibroblasts from a patient with a mutation in PTRF. Despite the complete clinical picture of a caveolinopathy, we found that caveolae in the CAV3-deficient myotubes were normal in shape and number. Furthermore, we found a difference in uptake of cholera toxin B between PTRF-deficient fibroblasts devoid of caveolae and normal fibroblasts. However, after caveolae were rescued by transfection of PTRF, cholera toxin B uptake did not normalize. We conclude that the presence of caveolae as an anatomic structure is not sufficient to ensure their proper function. Alternatively, the functional properties assigned to caveolae might be mediated by different mechanisms that have yet to be resolved.
authors.affiliation: Muscle Research Unit, Experimental and Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine Berlin, Berlin, Germany; and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Timmel
authors.affiliation: Muscle Research Unit, Experimental and Clinical Research Center, Charité Medical Faculty and Max Delbrück Center for Molecular Medicine Berlin, Berlin, Germany; and.
authors.forename: Séverine
authors.initials: S
authors.lastname: Kunz
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Seifert
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schuelke
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité Universitätsmedizin Berlin, Berlin, Germany simone.spuler@charite.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Spuler
mesh_terms: D016022:Case-Control Studies; D021941:Caveolae / Q000378:metabolism* / Q000648:ultrastructure; D051244:Caveolin 3 / Q000235:genetics / Q000378:metabolism; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000378:metabolism; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D046529:Microscopy, Electron, Transmission; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C417736:CAV3 protein, human; C497835:CAVIN1 protein, human; D051244:Caveolin 3; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D002772:Cholera Toxin
keywords: caveolae; caveolin; cavin 1/polymerase I and transcript release factor; electron microscopy; fluorescein-activated cell sorting