Literature DB >> 16445293

Alpha-RgIA: a novel conotoxin that specifically and potently blocks the alpha9alpha10 nAChR.

Michael Ellison1, Christian Haberlandt, María Eugenia Gomez-Casati, Maren Watkins, A Belén Elgoyhen, J Michael McIntosh, Baldomero M Olivera.   

Abstract

The alpha9 and alpha10 nicotinic acetylcholine receptor (nAChR) subunits assemble to form the alpha9alpha10 nAChR subtype. This receptor is believed to mediate cholinergic synaptic transmission between efferent olivocochlear fibers and the hair cells of the cochlea. In addition alpha9 and/or alpha10 expression has been described in dorsal root ganglion neurons, lymphocytes, skin keratinocytes, and the pars tuberalis of the pituitary. Specific antagonists that selectively block the alpha9alpha10 channel could be valuable tools for elucidating its role in these diverse tissues. This study describes a novel alpha-conotoxin from the Western Atlantic species Conus regius, alpha-conotoxin RgIA (alpha-RgIA), that is a subtype specific blocker of the alpha9alpha10 nAChR. alpha-RgIA belongs to the alpha4/3 subfamily of the alpha-conotoxin family; sequence and subtype specificity comparisons between alpha-RgIA and previously characterized alpha4/3 toxins indicate that the amino acids in the C-terminal half of alpha-RgIA are responsible for its preferential inhibition of the alpha9alpha10 nAChR subtype.

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Year:  2006        PMID: 16445293     DOI: 10.1021/bi0520129

Source DB:  PubMed          Journal:  Biochemistry        ISSN: 0006-2960            Impact factor:   3.162


  73 in total

1.  Critical residue properties for potency and selectivity of α-Conotoxin RgIA towards α9α10 nicotinic acetylcholine receptors.

Authors:  Peter N Huynh; Peta J Harvey; Joanna Gajewiak; David J Craik; J Michael McIntosh
Journal:  Biochem Pharmacol       Date:  2020-06-25       Impact factor: 5.858

2.  Molecular basis for the differential sensitivity of rat and human α9α10 nAChRs to α-conotoxin RgIA.

Authors:  Layla Azam; J Michael McIntosh
Journal:  J Neurochem       Date:  2012-08-03       Impact factor: 5.372

Review 3.  Genome mining for ribosomally synthesized natural products.

Authors:  Juan E Velásquez; Wilfred A van der Donk
Journal:  Curr Opin Chem Biol       Date:  2010-11-20       Impact factor: 8.822

4.  Characterization of a novel α-conotoxin TxID from Conus textile that potently blocks rat α3β4 nicotinic acetylcholine receptors.

Authors:  Sulan Luo; Dongting Zhangsun; Xiaopeng Zhu; Yong Wu; Yuanyan Hu; Sean Christensen; Peta J Harvey; Muharrem Akcan; David J Craik; J Michael McIntosh
Journal:  J Med Chem       Date:  2013-11-22       Impact factor: 7.446

5.  Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea.

Authors:  Isabelle Roux; Eric Wersinger; J Michael McIntosh; Paul A Fuchs; Elisabeth Glowatzki
Journal:  J Neurosci       Date:  2011-10-19       Impact factor: 6.167

6.  alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nicotinic acetylcholine receptors.

Authors:  Can Peng; Yuhong Han; Tanya Sanders; Geoffrey Chew; Jing Liu; Edward Hawrot; Chengwu Chi; Chunguang Wang
Journal:  Peptides       Date:  2008-06-07       Impact factor: 3.750

Review 7.  Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system.

Authors:  Antoine Taly; Pierre-Jean Corringer; Denis Guedin; Pierre Lestage; Jean-Pierre Changeux
Journal:  Nat Rev Drug Discov       Date:  2009-09       Impact factor: 84.694

8.  α9- and α7-containing receptors mediate the pro-proliferative effects of nicotine in the A549 adenocarcinoma cell line.

Authors:  Vanessa Mucchietto; Francesca Fasoli; Susanna Pucci; Milena Moretti; Roberta Benfante; Annalisa Maroli; Simona Di Lascio; Cristiano Bolchi; Marco Pallavicini; Cheryl Dowell; Michael McIntosh; Francesco Clementi; Cecilia Gotti
Journal:  Br J Pharmacol       Date:  2017-09-08       Impact factor: 8.739

9.  Scanning mutagenesis of alpha-conotoxin Vc1.1 reveals residues crucial for activity at the alpha9alpha10 nicotinic acetylcholine receptor.

Authors:  Reena Halai; Richard J Clark; Simon T Nevin; Jonas E Jensen; David J Adams; David J Craik
Journal:  J Biol Chem       Date:  2009-05-15       Impact factor: 5.157

Review 10.  Alpha-conotoxins as pharmacological probes of nicotinic acetylcholine receptors.

Authors:  Layla Azam; J Michael McIntosh
Journal:  Acta Pharmacol Sin       Date:  2009-05-18       Impact factor: 6.150

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