Journal article
Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors
The EMBO journal, Vol.23(9), pp.1922-1933
04/22/2004
DOI: 10.1038/sj.emboj.7600203
PMCID: PMC404323
PMID: 15103325
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
fab1
Δ-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
svp1
Δ 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 β-propellers, and the PtdIns(3,5)
P
2
-binding site is on the β-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.
Details
- Title: Subtitle
- Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors
- Creators
- Stephen K Dove - University of BirminghamRobert C Piper - University of IowaRobert K McEwen - University of BirminghamJong W Yu - Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA, USAMegan C King - University of PennsylvaniaDavid C Hughes - University of DerbyJan Thuring - University of CambridgeAndrew B Holmes - University of CambridgeFrank T Cooke - University College LondonRobert H Michell - University of BirminghamPeter J Parker - London Research InstituteMark A Lemmon - University of Pennsylvania
- Resource Type
- Journal article
- Publication Details
- The EMBO journal, Vol.23(9), pp.1922-1933
- DOI
- 10.1038/sj.emboj.7600203
- PMID
- 15103325
- PMCID
- PMC404323
- NLM abbreviation
- EMBO J
- ISSN
- 0261-4189
- eISSN
- 1460-2075
- Publisher
- Nature Publishing Group
- Alternative title
- WD-40 motifs can act as lipid-binding modules
- Language
- English
- Date published
- 04/22/2004
- Academic Unit
- Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984297508302771
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