Type Iγ phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with μ 1B adaptin

Kun Ling, Shawn F. Bairstow, Chateen Carbonara, Dmitry A. Turbin, David G. Huntsman, Richard A. Anderson

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Assembly of E-cadherin-based adherens junctions (AJ) is obligatory for establishment of polarized epithelia and plays a key role in repressing the invasiveness of many carcinomas. Here we show that type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) directly binds to E-cadherin and modulates E-cadherin trafficking. PIPKIγ also interacts with the μ subunits of clathrin adaptor protein (AP) complexes and acts as a signalling scaffold that links AP complexes to E-cadherin. Depletion of PIPKIγ or disruption of PIPKIγ binding to either E-cadherin or AP complexes results in defects in E-cadherin transport and blocks AJ assembly. An E-cadherin germline mutation that loses PIPKIγ binding and shows disrupted basolateral membrane targeting no longer forms AJs and leads to hereditary gastric cancers. These combined results reveal a novel mechanism where PIPKIγ serves as both a scaffold, which links E-cadherin to AP complexes and the trafficking machinery, and a regulator of trafficking events via the spatial generation of phosphatidylinositol-4,5-bisphosphate.

Original languageEnglish (US)
Pages (from-to)343-353
Number of pages11
JournalJournal of Cell Biology
Volume176
Issue number3
DOIs
StatePublished - Jan 29 2007
Externally publishedYes

Fingerprint

Adherens Junctions
Phosphatidylinositol Phosphates
Cadherins
Phosphotransferases
Vesicular Transport Adaptor Proteins
Germ-Line Mutation
Protein Transport
Phosphatidylinositols
Stomach Neoplasms
Epithelium
Carcinoma
Membranes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Type Iγ phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with μ 1B adaptin. / Ling, Kun; Bairstow, Shawn F.; Carbonara, Chateen; Turbin, Dmitry A.; Huntsman, David G.; Anderson, Richard A.

In: Journal of Cell Biology, Vol. 176, No. 3, 29.01.2007, p. 343-353.

Research output: Contribution to journalArticle

Ling, Kun ; Bairstow, Shawn F. ; Carbonara, Chateen ; Turbin, Dmitry A. ; Huntsman, David G. ; Anderson, Richard A. / Type Iγ phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with μ 1B adaptin. In: Journal of Cell Biology. 2007 ; Vol. 176, No. 3. pp. 343-353.
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