Ca2+-dependent regulation and binding of calmodulin to multiple sites of Transient Receptor Potential Melastatin 3 (TRPM3) ion channels. (July 2018)

• Record Type: Journal Article
• Authors: Przibilla, Julia; Dembla, Sandeep; Rizun, Oleksandr; Lis, Annette; Jung, Martin; Oberwinkler, Johannes; Beck, Andreas; Philipp, Stephan E.
• Is Part Of: Cell calcium. Volume 73(2018)
• Page Start: 40
• Page End: 52
• Publication Date: 2018-07
• Subjects: TRP transient receptor potential channels -- CaM calmodulin -- CaMmut calmodulin mutant -- CaMBS calmodulin binding site -- PregS pregnenolone sulfate -- EGFP enhanced green fluorescent protein -- GST glutathione-S-transferase; Transient receptor potential channels (TRP channels) -- Calcium -- Calmodulin (CaM) -- Transient Receptor Potential Melastatin 3 (TRPM3) -- IQ-motif; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2018.03.005
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Highlights: TRPM3 channel activity is strongly reduced by increased cytoplasmic Ca 2+ concentrations. CaM binds to the full-length TRPM3 channel and to theTRPM3 N-terminus in a Ca 2+ dependent manner. The TRPM3 amino terminus comprise at least five individual calmodulin binding sites (CaMBS). Lysine residues in CaMBS2 are part of an IQ-motif and important for CaM binding and TRPM3 stability. Abstract: TRPM3 proteins assemble to Ca 2+ -permeable cation channels in the plasma membrane, which act as nociceptors of noxious heat and mediators of insulin and cytokine release. Here we show that TRPM3 channel activity is strongly dependent on intracellular Ca 2+ . Conceivably, this effect is attributed to the Ca 2+ binding protein calmodulin, which binds to TRPM3 in a Ca 2+ -dependent manner. We identified five calmodulin binding sites within the amino terminus of TRPM3, which displayed different binding affinities in dependence of Ca 2+ . Mutations of lysine residues in calmodulin binding site 2 strongly reduced calmodulin binding and TRPM3 activity indicating the importance of this domain for TRPM3-mediated Ca 2+ signaling. Our data show that TRPM3 channels are regulated by intracellular Ca 2+ and provide the basis for a mechanistic understanding of the regulation of TRPM3 by calmodulin.