Please use this identifier to cite or link to this item: doi:10.22028/D291-39759
Title: Calmodulin Regulates Transient Receptor Potential TRPM3 and TRPM8-Induced Gene Transcription
Author(s): Thiel, Gerald
Rössler, Oliver G.
Language: German
Title: International Journal of Molecular Sciences
Volume: 24
Issue: 9
Publisher/Platform: MDPI
Year of Publication: 2023
Free key words: calmodulin
ophiobolin A
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Calmodulin is a small protein that binds Ca2+ ions via four EF-hand motifs. The Ca2+/ calmodulin complex as well as Ca2+-free calmodulin regulate the activities of numerous enzymes and ion channels. Here, we used genetic and pharmacological tools to study the functional role of calmodulin in regulating signal transduction of TRPM3 and TRPM8 channels. Both TRPM3 and TRPM8 are important regulators of thermosensation. Gene transcription triggered by stimulation of TRPM3 or TRPM8 channels was significantly impaired in cells expressing a calmodulin mutant with mutations in all four EF-hand Ca2+ binding motifs. Similarly, incubation of cells with the calmodulin inhibitor ophiobolin A reduced TRPM3 and TRPM8-induced signaling. The Ca2+/calmodulindependent protein phosphatase calcineurin was shown to negatively regulate TRPM3-induced gene transcription. Here, we show that TRPM8-induced transcription is also regulated by calcineurin. We propose that calmodulin plays a dual role in regulating TRPM3 and TRPM8 functions. Calmodulin is required for the activation of TRPM3 and TRPM8-induced intracellular signaling, most likely through a direct interaction with the channels. Ca2+ influx through TRPM3 and TRPM8 feeds back to TRPM3 and TRPM8-induced signaling by activation of the calmodulin-regulated enzyme calcineurin, which acts as a negative feedback loop for both TRPM3 and TRPM8 channel signaling.
DOI of the first publication: 10.3390/ijms24097902
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-397596
ISSN: 1422-0067
Date of registration: 16-May-2023
Faculty: M - Medizinische Fakultät
Department: M - Medizinische Biochemie und Molekularbiologie
Professorship: M - Prof. Dr. Gerald Thiel
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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