| | |  | | | | Record from Web of Science® | | | | | | |
| Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors |
|
|
| Author(s): Dove SK, Piper RC, McEwen RK, Yu JW, King MC, Hughes DC, Thuring J, Holmes AB, Cooke FT, Michell RH, Parker PJ, Lemmon MA |
| Source: EMBO JOURNAL Volume: 23 Issue: 9 Pages: 1922-1933 Published: MAY 5 2004 |
| Times Cited: 89 References: 51 |
| Abstract: Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P-2), made by Fab1p, is essential for vesicle recycling from vacuole/lysosomal compartments and for protein sorting into multivesicular bodies. To isolate PtdIns(3,5)P-2 effectors, we identified Saccharomyces cerevisiae mutants that display fab1Delta-like vacuole enlargement, one of which lacked the SVP1/YFR021w/ATG18 gene. Expressed Svp1p displays PtdIns(3,5)P-2 binding of exquisite specificity, GFP-Svp1p localises to the vacuole membrane in a Fab1p-dependent manner, and Svp1Delta cells fail to recycle a marker protein from the vacuole to the Golgi. Cells lacking Svp1p accumulate abnormally large amounts of PtdIns(3,5)P-2. These observations identify Svp1p as a PtdIns(3,5)P-2 effector required for PtdIns(3,5)P-2-dependent membrane recycling from the vacuole. Other Svp1p-related proteins, including human and Drosophila homologues, bind PtdIns(3,5)P-2 similarly. Svp1p and related proteins almost certainly fold as beta-propellers, and the PtdIns(3,5)P-2-binding site is on the beta-propeller. It is likely that many of the Svp1p-related proteins that are ubiquitous throughout the eukaryotes are PtdIns(3,5)P-2 effectors. Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P-2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P-2 effectors must exist. |
| Document Type: Article |
| Language: English |
| Reprint Address: Dove, SK (reprint author), Univ Birmingham, Dept Biosci, Sch Biosci, Birmingham B15 2TT, W Midlands England |
Addresses:
1. Univ Birmingham, Dept Biosci, Sch Biosci, Birmingham B15 2TT, W Midlands England
2. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA
3. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA
4. Univ Derby, Sch Environm & Appl Sci, Derby DE22 1GB, England
5. Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England
6. UCL, Dept Biochem & Mol Biol, London, England
7. Canc Res UK London Res Inst, Prot Phosphorylat Lab, London, England |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 821YP |
| ISSN: 0261-4189 |
| DOI: 10.1038/sj.emboj.7600203 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |