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PMID:18410729

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Citation

Schmitz, KR, Liu, J, Li, S, Setty, TG, Wood, CS, Burd, CG and Ferguson, KM (2008) Golgi localization of glycosyltransferases requires a Vps74p oligomer. Dev. Cell 14:523-34

Abstract

The mechanism of glycosyltransferase localization to the Golgi apparatus is a long-standing question in secretory cell biology. All Golgi glycosyltransferases are type II membrane proteins with small cytosolic domains that contribute to Golgi localization. To date, no protein has been identified that recognizes the cytosolic domains of Golgi enzymes and contributes to their localization. Here, we report that yeast Vps74p directly binds to the cytosolic domains of cis and medial Golgi mannosyltransferases and that loss of this interaction correlates with loss of Golgi localization of these enzymes. We have solved the X-ray crystal structure of Vps74p and find that it forms a tetramer, which we also observe in solution. Deletion of a critical structural motif disrupts tetramer formation and results in loss of Vps74p localization and function. Vps74p is highly homologous to the human GMx33 Golgi matrix proteins, suggesting a conserved function for these proteins in the Golgi enzyme localization machinery.

Links

PubMed PMC2707253 Online version:10.1016/j.devcel.2008.02.016

Keywords

Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Crystallography, X-Ray; Glycosylation; Glycosyltransferases/genetics; Glycosyltransferases/metabolism; Golgi Apparatus/chemistry; Golgi Apparatus/enzymology; HeLa Cells; Humans; Models, Molecular; Molecular Chaperones/genetics; Molecular Chaperones/metabolism; Molecular Sequence Data; Protein Structure, Quaternary; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Saccharomyces cerevisiae/cytology; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism

Significance

Annotations

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

YEAST:VPS74

located_in

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:VPS74

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:VPS74

involved_in

GO:0045053: protein retention in Golgi apparatus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:GOLP3

GO:0005794: Golgi apparatus

ECO:0000315:

C

Figure 7E. Without a particular beta-hairpin motif, the protein fails to localize to the golgi correctly.

complete
CACAO 9707

HUMAN:GOLP3

part_of

GO:0005794: Golgi apparatus

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:VPS74

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:VPS74

enables

GO:0019899: enzyme binding

ECO:0000353: physical interaction evidence used in manual assertion

SGD:S000000219
SGD:S000002891
SGD:S000003006
SGD:S000003722

F

Seeded From UniProt

complete

YEAST:VPS74

involved_in

GO:0034067: protein localization to Golgi apparatus

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:VPS74

GO:0006487: protein N-linked glycosylation

ECO:0000315:

P

Figure 1. KOs of the vps74 result in lack of mannosylation of various proteins

complete
CACAO 9716

YEAST:VPS74

GO:0035269: protein O-linked mannosylation

ECO:0000315:

P

Figure 1: KOs of vps74 result in lack of mannosylation of various proteins

complete
CACAO 9717

YEAST:VPS74

part_of

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:VPS74

involved_in

GO:0006487: protein N-linked glycosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:VPS74

involved_in

GO:0035269: protein O-linked mannosylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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