TY - JOUR
T1 - Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors
AU - Dove, Stephen
AU - Piper, RC
AU - McEwen, RK
AU - Yu, JW
AU - King, MC
AU - Hughes, DC
AU - Thuring, J
AU - Michell, Robert
PY - 2004/4/22
Y1 - 2004/4/22
N2 - 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 fab1delta-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 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)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 beta-propellers, and the PtdIns(3,5)P2-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)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.
AB - 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 fab1delta-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 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)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 beta-propellers, and the PtdIns(3,5)P2-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)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.
KW - AUT10
KW - lysosome
KW - ATG18
KW - phosphoinositide
KW - CVT18
UR - http://www.scopus.com/inward/record.url?scp=3142583199&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7600203
DO - 10.1038/sj.emboj.7600203
M3 - Article
C2 - 15103325
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
SN - 1460-2075
VL - 23
SP - 1922
EP - 1933
JO - The EMBO journal
JF - The EMBO journal
IS - 9
ER -