VPS13A and VPS13C are lipid transport proteins differentially localized at ER contact sites
| Autor: | Karin M. Reinisch, Marianna Leonzino, Joshua A. Lees, Florian A. Horenkamp, William Hancock-Cerutti, Heather E. Wheeler, Nikit Kumar, Pietro De Camilli, PeiQi Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Saccharomyces cerevisiae Proteins Endosome Saccharomyces cerevisiae Mitochondrion Biology Article 03 medical and health sciences Lipid droplet Organelle Late endosome Lipid Transport Research Articles Organelles Membranes Membrane transport protein Autophagy Cell Biology 3. Good health Cell biology nervous system diseases 030104 developmental biology Mitochondrial Membranes biology.protein lipids (amino acids peptides and proteins) Carrier Proteins |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Structural and biochemical studies show that VPS13 family proteins are lipid transporters. VPS13A and VPS13C tether the ER to mitochondria and to endosomes/lysosomes, respectively, suggesting lipid dyshomeostasis as the cause of chorea acanthocytosis and Parkinson’s disease resulting from their mutations. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|