Shin, JJH;
Liu, P;
Chan, LJ;
Ullah, A;
Pan, J;
Borchers, CH;
Burke, JE;
... Loewen, CJR; + view all
(2020)
pH Biosensing by PI4P Regulates Cargo Sorting at the TGN.
Developmental Cell
, 52
(4)
461-476.e4.
10.1016/j.devcel.2019.12.010.
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Abstract
Phosphoinositides, diacylglycerolpyrophosphate, ceramide-1-phosphate, and phosphatidic acid belong to a unique class of membrane signaling lipids that contain phosphomonoesters in their headgroups having pKa values in the physiological range. The phosphomonoester headgroup of phosphatidic acid enables this lipid to act as a pH biosensor as changes in its protonation state with intracellular pH regulate binding to effector proteins. Here, we demonstrate that binding of pleckstrin homology (PH) domains to phosphatidylinositol 4-phosphate (PI4P) in the yeast trans-Golgi network (TGN) is dependent on intracellular pH, indicating PI4P is a pH biosensor. pH biosensing by TGN PI4P in response to nutrient availability governs protein sorting at the TGN, likely by regulating sterol transfer to the TGN by Osh1, a member of the conserved oxysterol-binding protein (OSBP) family of lipid transfer proteins. Thus, pH biosensing by TGN PI4P allows for direct metabolic regulation of protein trafficking and cell growth.
| Type: | Article |
|---|---|
| Title: | pH Biosensing by PI4P Regulates Cargo Sorting at the TGN |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.devcel.2019.12.010 |
| Publisher version: | https://doi.org/10.1016/j.devcel.2019.12.010 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Osh1, PH domains, PI4P, Tat2, cytoplasmic pH, membrane contact sites, pH biosensing, phosphatidylinositol 4-phosphate, sterol trafficking, trans-Golgi Network |
| 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 Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10090502 |
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