VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites.

Autor:	Kumar N; Department of Cell Biology, Yale University School of Medicine, New Haven, CT., Leonzino M; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT., Hancock-Cerutti W; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT., Horenkamp FA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT., Li P; Department of Cell Biology, Yale University School of Medicine, New Haven, CT., Lees JA; Department of Cell Biology, Yale University School of Medicine, New Haven, CT., Wheeler H; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT., Reinisch KM; Department of Cell Biology, Yale University School of Medicine, New Haven, CT karin.reinisch@yale.edu., De Camilli P; Department of Cell Biology, Yale University School of Medicine, New Haven, CT pietro.decamilli@yale.edu.; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2018 Oct 01; Vol. 217 (10), pp. 3625-3639. Date of Electronic Publication: 2018 Aug 09.
DOI:	10.1083/jcb.201807019
Abstrakt:	Mutations in the human VPS13 genes are responsible for neurodevelopmental and neurodegenerative disorders including chorea acanthocytosis (VPS13A) and Parkinson's disease (VPS13C). The mechanisms of these diseases are unknown. Genetic studies in yeast hinted that Vps13 may have a role in lipid exchange between organelles. In this study, we show that the N-terminal portion of VPS13 is tubular, with a hydrophobic cavity that can solubilize and transport glycerolipids between membranes. We also show that human VPS13A and VPS13C bind to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes (VPS13C), and to lipid droplets (both VPS13A and VPS13C). These findings identify VPS13 as a lipid transporter between the ER and other organelles, implicating defects in membrane lipid homeostasis in neurological disorders resulting from their mutations. Sequence and secondary structure similarity between the N-terminal portions of Vps13 and other proteins such as the autophagy protein ATG2 suggest lipid transport roles for these proteins as well. (© 2018 Kumar et al.)
Databáze:	MEDLINE
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