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Oxidation of methio...
Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2
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- Fricke, Tabea C. (author)
- Hannover Medical School
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- Echtermeyer, Frank (author)
- Hannover Medical School
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- Zielke, Johannes (author)
- Hannover Medical School
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- de la Roche, Jeanne (author)
- Hannover Medical School
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- Filipovic, Milos R. (author)
- University of Bordeaux
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- Claverol, Stéphane (author)
- University of Bordeaux
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- Herzog, Christine (author)
- Hannover Medical School
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- Tominaga, Makoto (author)
- National Institutes of Natural Sciences
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- Pumroy, Ruth A. (author)
- University of Pennsylvania
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- Moiseenkova-Bell, Vera Y. (author)
- University of Pennsylvania
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- Zygmunt, Peter M. (author)
- Lund University,Lunds universitet,Neurofarmakologi och smärta,Forskargrupper vid Lunds universitet,Neuropharmacology and pain,Lund University Research Groups
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- Leffler, Andreas (author)
- Hannover Medical School
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- Eberhardt, Mirjam J. (author)
- Hannover Medical School
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(creator_code:org_t)
- 2019-11-12
- 2019
- English 7 s.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:48, s. 24359-24365
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http://dx.doi.org/10...
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https://www.pnas.org...
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Abstract
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- Thermosensitive transient receptor potential (TRP) ion channels detect changes in ambient temperature to regulate body temperature and temperature-dependent cellular activity. Rodent orthologs of TRP vanilloid 2 (TRPV2) are activated by nonphysiological heat exceeding 50 °C, and human TRPV2 is heat-insensitive. TRPV2 is required for phagocytic activity of macrophages which are rarely exposed to excessive heat, but what activates TRPV2 in vivo remains elusive. Here we describe the molecular mechanism of an oxidation-induced temperature-dependent gating of TRPV2. While high concentrations of H2O2 induce a modest sensitization of heat-induced inward currents, the oxidant chloramine-T (ChT), ultraviolet A light, and photosensitizing agents producing reactive oxygen species (ROS) activate and sensitize TRPV2. This oxidation-induced activation also occurs in excised inside-out membrane patches, indicating a direct effect on TRPV2. The reducing agent dithiothreitol (DTT) in combination with methionine sulfoxide reductase partially reverses ChT-induced sensitization, and the substitution of the methionine (M) residues M528 and M607 to isoleucine almost abolishes oxidation-induced gating of rat TRPV2. Mass spectrometry on purified rat TRPV2 protein confirms oxidation of these residues. Finally, macrophages generate TRPV2-like heat-induced inward currents upon oxidation and exhibit reduced phagocytosis when exposed to the TRP channel inhibitor ruthenium red (RR) or to DTT. In summary, our data reveal a methionine-dependent redox sensitivity of TRPV2 which may be an important endogenous mechanism for regulation of TRPV2 activity and account for its pivotal role for phagocytosis in macrophages.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Keyword
- Methionine
- Oxidation
- Phagocytosis
- Redox sensitivity
- TRPV2
Publication and Content Type
- art (subject category)
- ref (subject category)
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Fricke, Tabea C.
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Echtermeyer, Fra ...
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Zielke, Johannes
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de la Roche, Jea ...
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Filipovic, Milos ...
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Claverol, Stépha ...
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show more...
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Herzog, Christin ...
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Tominaga, Makoto
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Pumroy, Ruth A.
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Moiseenkova-Bell ...
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Zygmunt, Peter M ...
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Leffler, Andreas
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Eberhardt, Mirja ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Physiology
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Lund University