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PMID:20493815

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Citation

Mizuno-Yamasaki, E, Medkova, M, Coleman, J and Novick, P (2010) Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev. Cell 18:828-40

Abstract

Sec2p is the guanine nucleotide exchange factor (GEF) that activates the Rab GTPase Sec4p on secretory vesicles. Sec2p also binds a Rab acting earlier in the secretory pathway, Ypt32-GTP, forming a Rab GEF cascade. Ypt32p and the Sec4p effector Sec15p (a component of the exocyst complex) compete for binding to Sec2p. Indeed Ypt32p initially recruits Sec2p, but subsequently allows a handoff of active Sec2p/Sec4p to Sec15p. Intriguingly, Golgi-associated phosphatidylinositol 4-phosphate (PI4P) works together with Ypt32-GTP in this context. PI4P inhibits Sec2p-Sec15p interactions, promoting recruitment of Sec2p by Ypt32p as secretory vesicles form. However, PI4P levels appear to decline as vesicles reach secretory sites, allowing Sec15p to replace Ypt32p as vesicles mature. In this way, the regulation of PI4P levels may switch Sec2p/Sec4p function during vesicle maturation, from a Rab GEF recruitment cascade involving Ypt32p to an effector positive feedback loop involving Sec15p.

Links

PubMed PMC2877039 Online version:10.1016/j.devcel.2010.03.016

Keywords

1-Phosphatidylinositol 4-Kinase/genetics; 1-Phosphatidylinositol 4-Kinase/metabolism; Exocytosis/physiology; Golgi Apparatus/physiology; Guanine Nucleotide Exchange Factors/genetics; Guanine Nucleotide Exchange Factors/metabolism; Microscopy, Fluorescence; Mutation; Phosphatidylinositol Phosphates/metabolism; Saccharomyces cerevisiae/cytology; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/growth & development; Saccharomyces cerevisiae/physiology; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Vacuoles/physiology; rab GTP-Binding Proteins/genetics; rab GTP-Binding Proteins/metabolism; rab5 GTP-Binding Proteins/genetics; rab5 GTP-Binding Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:SEC2

located_in

GO:0005935: cellular bud neck

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:SEC2

located_in

GO:0005934: cellular bud tip

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:SEC2

part_of

GO:0005934: cellular bud tip

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:SEC2

part_of

GO:0005935: cellular bud neck

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:SEC2

enables

GO:0070273: phosphatidylinositol-4-phosphate binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:SEC2

enables

GO:0070273: phosphatidylinositol-4-phosphate binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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