Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
NRA-2, a nicalin homolog, regulates neuronal death by controlling surface localization of toxic Caenorhabditis elegans DEG/ENaC channels.
Kamat S
,
Yeola S
,
Zhang W
,
Bianchi L
,
Driscoll M
.
???displayArticle.abstract???
Hyperactivated DEG/ENaCs induce neuronal death through excessive cation influx and disruption of intracellular calcium homeostasis. Caenorhabditis elegans DEG/ENaC MEC-4 is hyperactivated by the (d) mutation and induces death of touch neurons. The analogous substitution in MEC-10 (MEC-10(d)) co-expressed in the same neurons is only mildly neurotoxic. We exploited the lower toxicity of MEC-10(d) to identify RNAi knockdowns that enhance neuronal death. We report here that knock-out of the C. elegans nicalin homolog NRA-2 enhances MEC-10(d)-induced neuronal death. Cell biological assays in C. elegans neurons show that NRA-2 controls the distribution of MEC-10(d) between the endoplasmic reticulum and the cell surface. Electrophysiological experiments in Xenopus oocytes support this notion and suggest that control of channel distribution by NRA-2 is dependent on the subunit composition. We propose that nicalin/NRA-2 functions in a quality control mechanism to retain mutant channels in the endoplasmic reticulum, influencing the extent of neuronal death. Mammalian nicalin may have a similar role in DEG/ENaC biology, therefore influencing pathological conditions like ischemia.
Almedom,
An ER-resident membrane protein complex regulates nicotinic acetylcholine receptor subunit composition at the synapse.
2009, Pubmed
Almedom,
An ER-resident membrane protein complex regulates nicotinic acetylcholine receptor subunit composition at the synapse.
2009,
Pubmed
Alvarez de la Rosa,
ENaC modulators and renal disease.
2013,
Pubmed
Bianchi,
The neurotoxic MEC-4(d) DEG/ENaC sodium channel conducts calcium: implications for necrosis initiation.
2004,
Pubmed
,
Xenbase
Bianchi,
Culture of embryonic C. elegans cells for electrophysiological and pharmacological analyses.
2006,
Pubmed
Brenner,
The genetics of Caenorhabditis elegans.
1974,
Pubmed
Brown,
MEC-2 and MEC-6 in the Caenorhabditis elegans sensory mechanotransduction complex: auxiliary subunits that enable channel activity.
2008,
Pubmed
,
Xenbase
Brown,
Gain-of-function mutations in the MEC-4 DEG/ENaC sensory mechanotransduction channel alter gating and drug blockade.
2007,
Pubmed
,
Xenbase
Calixto,
Enhanced neuronal RNAi in C. elegans using SID-1.
2010,
Pubmed
Chai,
Activation of acid-sensing ion channel 1a (ASIC1a) by surface trafficking.
2010,
Pubmed
Chatzigeorgiou,
Spatial asymmetry in the mechanosensory phenotypes of the C. elegans DEG/ENaC gene mec-10.
2010,
Pubmed
Chelur,
The mechanosensory protein MEC-6 is a subunit of the C. elegans touch-cell degenerin channel.
2002,
Pubmed
,
Xenbase
Christensen,
A primary culture system for functional analysis of C. elegans neurons and muscle cells.
2002,
Pubmed
Chu,
Acid-sensing ion channels in pathological conditions.
2013,
Pubmed
Dettmer,
Transmembrane protein 147 (TMEM147) is a novel component of the Nicalin-NOMO protein complex.
2010,
Pubmed
Driscoll,
Dying for a cause: invertebrate genetics takes on human neurodegeneration.
2003,
Pubmed
Driscoll,
The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration.
1991,
Pubmed
Eshcol,
Acid-sensing ion channel 3 (ASIC3) cell surface expression is modulated by PSD-95 within lipid rafts.
2008,
Pubmed
Fire,
Integrative transformation of Caenorhabditis elegans.
1986,
Pubmed
García-Añoveros,
Transport and localization of the DEG/ENaC ion channel BNaC1alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons.
2001,
Pubmed
Gessmann,
Molecular modeling of mechanosensory ion channel structural and functional features.
2010,
Pubmed
Goodman,
MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation.
2002,
Pubmed
,
Xenbase
Gottschalk,
Identification and characterization of novel nicotinic receptor-associated proteins in Caenorhabditis elegans.
2005,
Pubmed
Haffner,
Nicalin and its binding partner Nomo are novel Nodal signaling antagonists.
2004,
Pubmed
Hobbs,
Does epithelial sodium channel hyperactivity contribute to cystic fibrosis lung disease?
2013,
Pubmed
Hong,
In vivo structure-function analyses of Caenorhabditis elegans MEC-4, a candidate mechanosensory ion channel subunit.
2000,
Pubmed
Huang,
Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.
1994,
Pubmed
Huber,
Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels.
2006,
Pubmed
Kamath,
Effectiveness of specific RNA-mediated interference through ingested double-stranded RNA in Caenorhabditis elegans.
2001,
Pubmed
Kweon,
Acid-sensing ion channels (ASICs): therapeutic targets for neurological diseases and their regulation.
2013,
Pubmed
Luke,
An intracellular serpin regulates necrosis by inhibiting the induction and sequelae of lysosomal injury.
2007,
Pubmed
Martin-Fernandez,
A 'pocket guide' to total internal reflection fluorescence.
2013,
Pubmed
McCall,
Genetic control of necrosis - another type of programmed cell death.
2010,
Pubmed
O'Hagan,
The MEC-4 DEG/ENaC channel of Caenorhabditis elegans touch receptor neurons transduces mechanical signals.
2005,
Pubmed
Sangaletti,
A method for culturing embryonic C. elegans cells.
2013,
Pubmed
Sedensky,
A stomatin and a degenerin interact in lipid rafts of the nervous system of Caenorhabditis elegans.
2004,
Pubmed
Sendrowski,
Study of the protective effect of calcium channel blockers against neuronal damage induced by glutamate in cultured hippocampal neurons.
2013,
Pubmed
Shah,
Nicastrin functions as a gamma-secretase-substrate receptor.
2005,
Pubmed
Shreffler,
The unc-8 and sup-40 genes regulate ion channel function in Caenorhabditis elegans motorneurons.
1995,
Pubmed
Syntichaki,
Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans.
2002,
Pubmed
Wang,
Neurotoxic unc-8 mutants encode constitutively active DEG/ENaC channels that are blocked by divalent cations.
2013,
Pubmed
,
Xenbase
Xiong,
Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.
2004,
Pubmed
Xu,
Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum.
2001,
Pubmed
Yamashima,
Ca2+-dependent proteases in ischemic neuronal death: a conserved 'calpain-cathepsin cascade' from nematodes to primates.
2004,
Pubmed
Yermolaieva,
Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a.
2004,
Pubmed
Zhang,
MEC-2 is recruited to the putative mechanosensory complex in C. elegans touch receptor neurons through its stomatin-like domain.
2004,
Pubmed
,
Xenbase
Zhang,
Intersubunit interactions between mutant DEG/ENaCs induce synthetic neurotoxicity.
2008,
Pubmed
,
Xenbase
