ArticleThe Journal of biological chemistry2012
Molecular determinants of Gem protein inhibition of P/Q-type Ca2+ channels.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Direct crosstalk between GPCRs and ion channels via G proteins.Experimental & molecular medicine · 2025Review
- Inactivation influences the extent of inhibition of voltage-gated CaFrontiers in physiology · 2023Article
- Into the spotlight: RGK proteins in skeletal muscle.Cell calcium · 2021Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- Similar molecular determinants on Rem mediate two distinct modes of inhibition of CaChannels (Austin, Tex.) · 2016Article
- MEC-10 and MEC-19 Reduce the Neurotoxicity of the MEC-4(d) DEG/ENaC Channel in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2016Article
- Functional assessment of three Rem residues identified as critical for interactions with Ca(2+) channel β subunits.Pflugers Archiv : European journal of physiology · 2015Article
- Solution NMR and calorimetric analysis of Rem2 binding to the Ca2+ channel β4 subunit: a low affinity interaction is required for inhibition of Cav2.1 Ca2+ currents.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- RGK regulation of voltage-gated calcium channels.Science China. Life sciences · 2015Review
- Structure-function of proteins interacting with the α1 pore-forming subunit of high-voltage-activated calcium channels.Frontiers in physiology · 2014Review
- Regulation of voltage-dependent calcium channels by RGK proteins.Biochimica et biophysica acta · 2013Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The RGK family of monomeric GTP-binding proteins potently inhibits high voltage-activated Ca(2+) channels. The molecular mechanisms of this inhibition are largely unclear. In Xenopus oocytes, Gem suppresses the activity of P/Q-type Ca(2+) channels on the plasma membrane. This is presumed to occur through direct interactions of one or more Gem inhibitory sites and the pore-forming Ca(v)2.1 subunit in a manner dependent on the Ca(2+) channel subunit β (Ca(v)β). In this study we investigated the molecular determinants in Gem that are critical for this inhibition. Like other RGK proteins, Gem contains a conserved Ras-like core and extended N and C termini. A 12-amino acid fragment in the C terminus was found to be crucial for and sufficient to produce Ca(v)β-dependent inhibition, suggesting that this region forms an inhibitory site. A three-amino acid motif in the core was also found to be critical, possibly forming another inhibitory site. Mutating either site individually did not hamper Gem inhibition, but mutating both sites together completely abolished Gem inhibition without affecting Gem protein expression level or disrupting Gem interaction with Ca(v)2.1 or Ca(v)β. Mutating Gem residues that are crucial for interactions with previously demonstrated RGK modulators such as calmodulin, 14-3-3, and phosphatidylinositol lipids did not significantly affect Gem inhibition. These results suggest that Gem contains two candidate inhibitory sites, each capable of producing full inhibition of P/Q-type Ca(2+) channels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.