Type I[gamma] phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with [mu]1B adaptin.
Ling, Kun 1; Bairstow, Shawn F. 1; Carbonara, Chateen 1; Turbin, Dmitry A. 2; Huntsman, David G. 2; Anderson, Richard A. 1
[Article] Journal of Cell Biology. 176(3):343-353, January 29, 2007.

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: 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 I[gamma] phosphatidylinositol phosphate kinase (PIPKI[gamma]) directly binds to E-cadherin and modulates E-cadherin trafficking. PIPKI[gamma] also interacts with the [mu] subunits of clathrin adaptor protein (AP) complexes and acts as a signalling scaffold that links AP complexes to E-cadherin. Depletion of PIPKI[gamma] or disruption of PIPKI[gamma] 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 PIPKI[gamma] 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 PIPKI[gamma] 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.

Copyright (C) 2007, The Rockefeller University Press