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.
Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor / Minogue, Shane; Waugh, Mark G.; DE MATTEIS, Maria Antonietta; Stephens, David J.; Berditchevski, Fedor; Hsuan, Justin J.. - In: JOURNAL OF CELL SCIENCE. - ISSN 0021-9533. - 119:3(2006), pp. 571-580. [10.1242/jcs.02752]
Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor
DE MATTEIS, Maria Antonietta;
2006
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.