Article
- The EMBO Journal (2004) 23, 1922 - 1933
- doi:10.1038/sj.emboj.7600203
Published online: 22 April 2004
Subject Category:
Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors
Stephen K Dove1, Robert C Piper2, Robert K McEwen1, Jong W Yu3, Megan C King3, David C Hughes4, Jan Thuring5, Andrew B Holmes5, Frank T Cooke6, Robert H Michell1, Peter J Parker7 and Mark A Lemmon3
- School of Biosciences, University of Birmingham, Birmingham, UK
- Department of Physiology and Biophysics, University of Iowa, Iowa City, IA, USA
- Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
- School of Environmental and Applied Sciences, University of Derby, Derby, UK
- Department of Chemistry, University of Cambridge, Cambridge, UK
- Department of Biochemistry & Molecular Biology, University College London, London, UK
- Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, UK
Correspondence to:
Stephen K Dove, Department of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. Tel.: +44 121 414 8513; Fax: +44 121 414 7816; E-mail: s.k.dove@bham.ac.uk
Received 26 August 2003; Accepted 15 March 2004
Abstract
Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), made by Fab1p, is essential for vesicle recycling from vacuole/lysosomal compartments and for protein sorting into multivesicular bodies. To isolate PtdIns(3,5)P2 effectors, we identified Saccharomyces cerevisiae mutants that display fab1
-like vacuole enlargement, one of which lacked the SVP1/YFR021w/ATG18 gene. Expressed Svp1p displays PtdIns(3,5)P2 binding of exquisite specificity, GFP-Svp1p localises to the vacuole membrane in a Fab1p-dependent manner, and svp1 cells fail to recycle a marker protein from the vacuole to the Golgi. Cells lacking Svp1p accumulate abnormally large amounts of PtdIns(3,5)P2. These observations identify Svp1p as a PtdIns(3,5)P2 effector required for PtdIns(3,5)P2-dependent membrane recycling from the vacuole. Other Svp1p-related proteins, including human and Drosophila homologues, bind PtdIns(3,5)P2 similarly. Svp1p and related proteins almost certainly fold as 
-propellers, and the PtdIns(3,5)P2-binding site is on the -propeller. It is likely that many of the Svp1p-related proteins that are ubiquitous throughout the eukaryotes are PtdIns(3,5)P2 effectors. Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P2 effectors must exist.
Keywords:
- ATG18,
- CVT18,
- AUT10,
- lysosome,
- phosphoinositide
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