Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor.
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 IIalpha 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 IIalpha activity was inhibited in vivo using the monoclonal antibody 4C5G or by depression of endogenous phosphatidylinositol 4-kinase IIalpha 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 IIalpha is necessary for the correct endocytic traffic and downregulation of activated epidermal growth factor receptor.
Minogue
Shane
S
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. s.minogue@medsch.ucl.ac.uk
Waugh
Mark G
MG
De Matteis
Maria Antonietta
MA
Stephens
David J
DJ
Berditchevski
Fedor
F
Hsuan
J Justin
JJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D011992:Endosomes / Q000201:enzymology*; D066246:ErbB Receptors / Q000378:metabolism*; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; D017853:Phosphotransferases (Alcohol Group Acceptor); C402182:phosphatidylinositol phosphate 4-kinase; D066246:ErbB Receptors