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First published online January 27, 2006
doi: 10.1242/10.1242/jcs.02752

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Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor

¹ Centre for Molecular Cell Biology, Department of Medicine, Royal Free and University College Medical School, University College London, Rowland Hill Street, London, NW3 2PF, UK
² Department of Cell Biology and Oncology, Consorzio Mario Negri Sud, Via Nazionale, 66030 Santa Maria Imbaro (Chieti), Italy
³ Department of Biochemistry, University of Bristol, School of Medical Sciences, University Walk, Bristol, BS8 1TD, UK
⁴ CRUK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TA, UK

^* Author for correspondence (e-mail: s.minogue{at}medsch.ucl.ac.uk)

Accepted 20 October 2005

The type II alpha isoform of phosphatidylinositol 4-kinase has recently been shown to function in the recruitment of adaptor protein-1 complexes to the trans-Golgi network. Here we show that phosphatidylinositol 4-kinase II is also a component of highly dynamic membranes of the endosomal system where it colocalises with protein markers of the late endosome and with endocytosed epidermal growth factor. When phosphatidylinositol 4-kinase II activity was inhibited in vivo using the monoclonal antibody 4C5G or by depression of endogenous phosphatidylinositol 4-kinase II protein levels using RNA interference, ligand-bound epidermal growth factor receptor failed to traffic to late endosomes and instead accumulated in vesicles in a sub-plasma membrane compartment. Furthermore, lysosomal degradation of activated epidermal growth factor receptor was dramatically impaired in small inhibitory RNA-treated cells. We demonstrate that phosphatidylinositol 4-kinase II is necessary for the correct endocytic traffic and downregulation of activated epidermal growth factor receptor.

Key words: Type II phosphatidylinositol 4-kinase, Endocytosis, Degradation, Epidermal growth factor

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