PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal

Jing Wang, Hui Qiao Sun, Eric Macia, Tomas Kirchhausen, Hadiya Watson, Juan S. Bonifacino, Helen L. Yin

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Phosphatidylinositol 4 phosphate (PI4P) is highly enriched in the trans-Golgi network (TGN). Here we establish that PI4P is a key regulator of the recruitment of the GGA clathrin adaptor proteins to the TGN and that PI4P has a novel role in promoting their recognition of the ubiquitin (Ub) sorting signal. Knockdown of PI4KIIα by RNA interference (RNAi), which depletes the TGN's PI4P, impaired the recruitment of the GGAs to the TGN. GGAs bind PI4P primarily through their GAT domain, in a region called C-GAT, which also binds Ub but not Arfl. We identified two basic residues in the GAT domain that are essential for PI4P binding in vitro and for the recruitment of GGAs to the TGN in vivo. Unlike wild-type GGA, GGA with mutated GATs failed to rescue the abnormal TGN phenotype of the GGA RNAi-depleted cells. These residues partially overlap with those that bind Ub, and PI4P increased the affinity of the GAT domain for Ub. Because the recruitment of clathrin adaptors and their cargoes to the TGN is mediated through a web of low-affinity interactions, our results show that the dual roles of PI4P can promote specific GGA targeting and cargo recognition at the TGN.

Original languageEnglish (US)
Pages (from-to)2646-2655
Number of pages10
JournalMolecular Biology of the Cell
Volume18
Issue number7
DOIs
StatePublished - Jul 2007

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trans-Golgi Network
Ubiquitin
Vesicular Transport Adaptor Proteins
RNA Interference
phosphatidylinositol 4-phosphate
GGA adaptor proteins
GAT
Phenotype

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal. / Wang, Jing; Sun, Hui Qiao; Macia, Eric; Kirchhausen, Tomas; Watson, Hadiya; Bonifacino, Juan S.; Yin, Helen L.

In: Molecular Biology of the Cell, Vol. 18, No. 7, 07.2007, p. 2646-2655.

Research output: Contribution to journalArticle

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