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J. Am. Chem. Soc., May 28 2025, 147 (21) | https://doi.org/10.1021/jacs.4c16206
Pools of Independently Cycling Inositol Phosphates Revealed by Pulse Labeling with 18O-Water
Geun-Don Kim 1, Guizhen Liu 2,3, Danye Qiu 2, Maria Giovanna De Leo 1, Navin Gopaldass 1, Jacques Hermes 3,4, Jens Timmer 3,4, Adolfo Saiardi 5, Andreas Mayer 1, Henning Jacob Jessen 2,3
1Département d'immunobiologie, Université de Lausanne, CH-1066 Epalinges, Switzerland.
2Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany.
3CIBSS─Centre for Integrative Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.
4Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.
5Medical Research Council, Laboratory for Molecular Cell Biology, University College London, WC1E 6BT London, U.K.
G.-D.K. and G.L. contributed equally to this work.
Corresponding Authors: Andreas Mayer, Henning Jacob Jessen
1Département d'immunobiologie, Université de Lausanne, CH-1066 Epalinges, Switzerland.
2Institute of Organic Chemistry, University of Freiburg, 79104 Freiburg, Germany.
3CIBSS─Centre for Integrative Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.
4Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.
5Medical Research Council, Laboratory for Molecular Cell Biology, University College London, WC1E 6BT London, U.K.
G.-D.K. and G.L. contributed equally to this work.
Corresponding Authors: Andreas Mayer, Henning Jacob Jessen
Abstract
Inositol phosphates control many central processes in eukaryotic cells including nutrient availability, growth, and motility. Kinetic resolution of a key modulator of their signaling functions, the turnover of the phosphate groups on the inositol ring, has been hampered by slow uptake, high dilution, and constraining growth conditions in radioactive pulse-labeling approaches. Here, we demonstrate a rapid (seconds to minutes) and nonradioactive labeling strategy of inositol polyphosphates through18O-water in yeast, human cells, and amoeba, which can be applied in any media. In combination with capillary electrophoresis and mass spectrometry,18O-water labeling simultaneously dissects the in vivo phosphate group dynamics of a broad spectrum of even rare inositol phosphates. The good temporal resolution allowed us to discover vigorous phosphate group exchanges in some inositol polyphosphates and pyrophosphates, whereas others remain remarkably inert. We propose a model in which the biosynthetic pathway of inositol polyphosphates and pyrophosphates is organized in distinct, kinetically separated pools. While transfer of compounds between those pools is slow, each pool undergoes rapid internal phosphate cycling. This might enable the pools to perform distinct signaling functions while being metabolically connected.
논문정보
- Research article
- 2025년 05월 (BRIC 등록일 2025-06-11)
- 국외 연구진
- 바이오·의료융합 > 다학제 융합/복합
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