ArticleProceedings of the National Academy of Sciences of the United States of America2010
Direct inhibition of P/Q-type voltage-gated Ca2+ channels by Gem does not require a direct Gem/Cavbeta interaction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Molecular Partners of Voltage-Gated Calcium Channel β and αThe Journal of membrane biology · 2026Review
- Inactivation influences the extent of inhibition of voltage-gated CaFrontiers in physiology · 2023Article
- Into the spotlight: RGK proteins in skeletal muscle.Cell calcium · 2021Review
- Article
- Engineering selectivity into RGK GTPase inhibition of voltage-dependent calcium channels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Defining the MO's of RGK proteins.Channels (Austin, Tex.) · 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
- The role of auxiliary subunits for the functional diversity of voltage-gated calcium channels.Journal of cellular physiology · 2015Review
- 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
- Nerve injury induces a Gem-GTPase-dependent downregulation of P/Q-type Ca2+ channels contributing to neurite plasticity in dorsal root ganglion neurons.Pflugers Archiv : European journal of physiology · 2015Article
- RGK regulation of voltage-gated calcium channels.Science China. Life sciences · 2015Review
- BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked exocytosis.The Journal of cell biology · 2014Article
- Ancient origins of RGK protein function: modulation of voltage-gated calcium channels preceded the protostome and deuterostome split.PloS one · 2014Article
- 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
- Bio-inspired voltage-dependent calcium channel blockers.Nature communications · 2013Article
- Article
- Calcium channel auxiliary α2δ and β subunits: trafficking and one step beyond.Nature reviews. Neuroscience · 2012Review
- Molecular determinants of Gem protein inhibition of P/Q-type Ca2+ channels.The Journal of biological chemistry · 2012Article
- Activity-dependent subcellular cotrafficking of the small GTPase Rem2 and Ca2+/CaM-dependent protein kinase IIα.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Rem, Rem2, Rad, and Gem/Kir (RGK) family of small GTP-binding proteins potently inhibits high voltage-activated (HVA) Ca(2+) channels, providing a powerful means of modulating neural, endocrine, and muscle functions. The molecular mechanisms of this inhibition are controversial and remain largely unclear. RGK proteins associate directly with Ca(2+) channel beta subunits (Ca(v)beta), and this interaction is widely thought to be essential for their inhibitory action. In this study, we investigate the molecular underpinnings of Gem inhibition of P/Q-type Ca(2+) channels. We find that a purified Gem protein markedly and acutely suppresses P/Q channel activity in inside-out membrane patches, that this action requires Ca(v)beta but not the Gem/Ca(v)beta interaction, and that Gem coimmunoprecipitates with the P/Q channel alpha(1) subunit (Ca(v)alpha(1)) in a Ca(v)beta-independent manner. By constructing chimeras between P/Q channels and Gem-insensitive low voltage-activated T-type channels, we identify a region encompassing transmembrane segments S1, S2, and S3 in the second homologous repeat of Ca(v)alpha(1) critical for Gem inhibition. Exchanging this region between P/Q and T channel Ca(v)alpha(1) abolishes Gem inhibition of P/Q channels and confers Ca(v)beta-dependent Gem inhibition to a chimeric T channel that also carries the P/Q I-II loop (a cytoplasmic region of Ca(v)alpha(1) that binds Ca(v)beta). Our results challenge the prevailing view regarding the role of Ca(v)beta in RGK inhibition of high voltage-activated Ca(2+) channels and prompt a paradigm in which Gem directly binds and inhibits Ca(v)beta-primed Ca(v)alpha(1) on the plasma membrane.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.