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Title

TipC and the chorea-acanthocytosis protein VPS13A regulate autophagy in Dictyostelium and human HeLa cells

AuthorsMuñoz-Braceras, Sandra ; Calvo, Rosa M. ; Escalante, Ricardo
Issue Date2015
PublisherTaylor & Francis
CitationAutophagy 11(6): 918-927 (2015)
AbstractDeficient autophagy causes a distinct phenotype in Dictyostelium discoideum, characterized by the formation of multitips at the mound stage. This led us to analyze autophagy in a number of multitipped mutants described previously (tipA¯, tipB¯, tipC¯, and tipD¯). We found a clear autophagic dysfunction in tipC¯ and tipD¯ while the others showed no defects. tipD codes for a homolog of Atg16, which confirms the role of this protein in Dictyostelium autophagy and validates our approach. The tipC-encoded protein is highly similar to human VPS13A (also known as chorein), whose mutations cause the chorea-acanthocytosis syndrome. No member of the VPS13 protein family has been previously related to autophagy despite the presence of a region of similarity to Atg2 at the C terminus. This region also contains the conserved domain of unknown function DUF1162. Of interest, the expression of the TipC Cterminal coding sequence containing these 2 motifs largely complemented the mutant phenotype. Dictyostelium cells lacking TipC displayed a reduced number of autophagosomes visualized with the markers GFP-Atg18 and GFP-Atg8 and an impaired autophagic degradation as determined by a proteolytic cleavage assay. Downregulation of human VPS13A in HeLa cells by RNA interference confirmed the participation of the human protein in autophagy. VPS13Adepleted cells showed accumulation of autophagic markers and impaired autophagic flux.
Publisher version (URL)https://doi.org/10.1080/15548627.2015.1034413
URIhttp://hdl.handle.net/10261/154464
DOI10.1080/15548627.2015.1034413
Identifiersdoi: 10.1080/15548627.2015.1034413
e-issn: 1554-8635
issn: 1554-8627
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