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PMID:18193037

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Citation

Franch-Marro, X, Wendler, F, Guidato, S, Griffith, J, Baena-Lopez, A, Itasaki, N, Maurice, MM and Vincent, JP (2008) Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nat. Cell Biol. 10:170-7

Abstract

The glycolipoproteins of the Wnt family raise interesting trafficking issues, especially with respect to spreading within tissues. Recently, the retromer complex has been suggested to participate in packaging Wnts into long-range transport vehicles. Our analysis of a Drosophila mutant in Vps35 show that, instead, the retromer complex is required for efficient progression of Wingless (a Drosophila Wnt) through the secretory pathway. Indeed expression of senseless, a short-range target gene, is lost in Vps35-deficient imaginal discs. In contrast, Vps35 is not required for Hedgehog secretion, suggesting specificity. Overexpression of Wntless, a transmembrane protein known to be specifically required for Wingless secretion overcomes the secretion block of Vps35-mutant cells. Furthermore, biochemical evidence confirms that Wntless engages with the retromer complex. We propose that Wntless accompanies Wingless to the plasma membrane where the two proteins dissociate. Following dissociation from Wingless, Wntless is internalized and returns to the Golgi apparatus in a retromer-dependent manner. Without the retromer-dependent recycling route, Wingless secretion is impaired and, as electron microscopy suggests, Wntless is diverted to a degradative compartment.

Links

PubMed Online version:10.1038/ncb1678

Keywords

Animals; Drosophila/genetics; Drosophila/metabolism; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila Proteins/secretion; Endosomes/metabolism; Golgi Apparatus/metabolism; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Intracellular Signaling Peptides and Proteins/metabolism; Membrane Proteins/metabolism; Mutation; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Protein Transport; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/secretion; Transcription Factors/genetics; Transcription Factors/metabolism; Vesicular Transport Proteins/genetics; Wnt1 Protein

Significance

Annotations

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

HUMAN:VP26A

part_of

GO:0030904: retromer complex

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

DROME:WNTG

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q95ST2

F

Seeded From UniProt

complete

DROME:Q7KVL7

involved_in

GO:0061357: positive regulation of Wnt protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q95RP4

involved_in

GO:0061357: positive regulation of Wnt protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:WLS

involved_in

GO:0061355: Wnt protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:WLS

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:WLS

involved_in

GO:0033157: regulation of intracellular protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:WLS

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P09615

F

Seeded From UniProt

complete

DROME:WLS

involved_in

GO:0050714: positive regulation of protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:VPS35

involved_in

GO:0031647: regulation of protein stability

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:Q5T9L3)

Seeded From UniProt

complete

HUMAN:VPS35

part_of

GO:0030904: retromer complex

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HUMAN:VPS35

involved_in

GO:0042147: retrograde transport, endosome to Golgi

ECO:0000303: author statement without traceable support used in manual assertion

P

  • transports_or_maintains_localization_of:(UniProtKB:Q5T9L3)

Seeded From UniProt

complete

DROME:Q9W277

involved_in

GO:0061357: positive regulation of Wnt protein secretion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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