Henmi, Y;
Morikawa, Y;
Oe, N;
Ikeda, N;
Fujita, A;
Takei, K;
Minogue, S;
(2016)
PtdIns4KII alpha generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes.
Molecular Biology Of The Cell
, 27
(6)
pp. 990-1001.
10.1091/mbc.E15-08-0564.
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Abstract
Phosphatidylinositol 4-kinase IIα (PtdIns4KIIα) localizes to the trans-Golgi network and endosomal compartments and has been implicated in the regulation of endosomal traffic, but the roles of both its enzymatic activity and the site of its action have not been elucidated. This study shows that PtdIns4KIIα is required for production of endosomal phosphatidylinositol 4-phosphate (PtdIns(4)P) on early endosomes and for the sorting of transferrin and epidermal growth factor receptor into recycling and degradative pathways. Depletion of PtdIns4KIIα with small interfering RNA significantly reduced the amount of vesicular PtdIns(4)P on early endosomes but not on Golgi membranes. Cells depleted of PtdIns4KIIα had an impaired ability to sort molecules destined for recycling from early endosomes. We further identify the Eps15 homology domain–containing protein 3 (EHD3) as a possible endosomal effector of PtdIns4KIIα. Tubular endosomes containing EHD3 were shortened and became more vesicular in PtdIns4KIIα-depleted cells. Endosomal PtdIns(4,5)P2 was also significantly reduced in PtdIns4KIIα-depleted cells. These results show that PtdIns4KIIα regulates receptor sorting at early endosomes through a PtdIns(4)P-dependent pathway and contributes substrate for the synthesis of endosomal PtdIns(4,5)P2.
| Type: | Article |
|---|---|
| Title: | PtdIns4KII alpha generates endosomal PtdIns(4)P and is required for receptor sorting at early endosomes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1091/mbc.E15-08-0564 |
| Publisher version: | http://dx.doi.org/10.1091/mbc.E15-08-0564 |
| Language: | English |
| Additional information: | © 2016 Henmi, Morikawa, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0) |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, Phosphatidylinositol 4-kinase Activity, Oxysterol Binding-protein, Plasma-membrane, Endocytic Pathway, Ii-alpha, Vesicular Compartments, Homology Domain, Cell Regulation, Ehd Proteins, Golgi |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Education |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1479573 |
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