title: Caveolin-1 is an aggresome-inducing protein.
abstract: Caveolin-1 (Cav1) drives the formation of flask-shaped membrane invaginations known as caveolae that participate in signaling, clathrin-independent endocytosis and mechanotransduction. Overexpression or mutations of Cav1 can lead to its mistrafficking, including its accumulation in a perinuclear compartment previously identified as the Golgi complex. Here, we show that in the case of overexpressed Cav1-GFP, this perinuclear compartment consists of cytoplasmic inclusion bodies generated in response to the accumulation of aggregates of misfolded proteins, known as aggresomes. Aggresomes containing Cav1-GFP are encased within vimentin cages, form in a microtubule-dependent manner, and are enriched in a number of key regulators of protein turnover, including ubiquitin, VCP/p97 and proteasomes. Interestingly, aggresome induction was cell-type dependent and was observed for many but not all Cav1 constructs tested. Furthermore, endogenous Cav1 accumulated in aggresomes formed in response to proteosomal inhibition. Our finding that Cav1 is both an aggresome-inducing and aggresome-localized protein provides new insights into how cells handle and respond to misfolded Cav1. They also raise the possibility that aggresome formation may contribute to some of reported phenotypes associated with overexpressed and/or mutant forms of Cav1.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Tiwari
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Copeland
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Raghunathan
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Epithelial Biology Program, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Chemical and Physical Biology Program, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Anne K
authors.initials: AK
authors.lastname: Kenworthy
mesh_terms: D000818:Animals; D019556:COS Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D040542:Mechanotransduction, Cellular; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D009928:Organ Specificity; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D066329:Protein Aggregates; D021381:Protein Transport; D013312:Stress, Physiological; D054875:Ubiquitination
chemical_list: D051242:Caveolin 1; D066329:Protein Aggregates; D046988:Proteasome Endopeptidase Complex