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CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion channel in Caenorhabditis elegans.
Tanis JE, Ma Z, Krajacic P, He L, Foskett JK, Lamitina T.
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Disruption of neuronal Ca(2+) homeostasis contributes to neurodegenerative diseases through mechanisms that are not fully understood. A polymorphism in CALHM1, a recently described ion channel that regulates intracellular Ca(2+) levels, is a possible risk factor for late-onset Alzheimer's disease. Since there are six potentially redundant CALHM family members in humans, the physiological and pathophysiological consequences of CALHM1 function in vivo remain unclear. The nematode Caenorhabditis elegans expresses a single CALHM1 homolog, CLHM-1. Here we find that CLHM-1 is expressed at the plasma membrane of sensory neurons and muscles. Like human CALHM1, C. elegans CLHM-1 is a Ca(2+)-permeable ion channel regulated by voltage and extracellular Ca(2+). Loss of clhm-1 in the body-wall muscles disrupts locomotory kinematics and biomechanics, demonstrating that CLHM-1 has a physiologically significant role in vivo. The motility defects observed in clhm-1 mutant animals can be rescued by muscle-specific expression of either C. elegans CLHM-1 or human CALHM1, suggesting that the function of these proteins is conserved in vivo. Overexpression of either C. elegans CLHM-1 or human CALHM1 in neurons is toxic, causing degeneration through a necrotic-like mechanism that is partially Ca(2+) dependent. Our data show that CLHM-1 is a functionally conserved ion channel that plays an important but potentially toxic role in excitable cell function.
Bamber,
The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor.
1999, Pubmed,
Xenbase
Bamber,
The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor.
1999,
Pubmed
,
Xenbase Bargmann,
Neurobiology of the Caenorhabditis elegans genome.
1998,
Pubmed Beecham,
CALHM1 polymorphism is not associated with late-onset Alzheimer disease.
2009,
Pubmed Berridge,
Calcium--a life and death signal.
1998,
Pubmed Bertram,
No association between CALHM1 and Alzheimer's disease risk.
2008,
Pubmed Bezprozvanny,
Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease.
2008,
Pubmed Boada,
CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease in a recessive model.
2010,
Pubmed Bootman,
2-aminoethoxydiphenyl borate (2-APB) is a reliable blocker of store-operated Ca2+ entry but an inconsistent inhibitor of InsP3-induced Ca2+ release.
2002,
Pubmed Boulay,
Cloning and expression of a novel mammalian homolog of Drosophila transient receptor potential (Trp) involved in calcium entry secondary to activation of receptors coupled by the Gq class of G protein.
1997,
Pubmed Brenner,
The genetics of Caenorhabditis elegans.
1974,
Pubmed Carre-Pierrat,
The SLO-1 BK channel of Caenorhabditis elegans is critical for muscle function and is involved in dystrophin-dependent muscle dystrophy.
2006,
Pubmed Catterall,
Structure and function of voltage-gated ion channels.
1993,
Pubmed Chalfie,
The neural circuit for touch sensitivity in Caenorhabditis elegans.
1985,
Pubmed Chung,
A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C. elegans.
2000,
Pubmed Coe,
Calcium binding chaperones of the endoplasmic reticulum.
2009,
Pubmed Dreses-Werringloer,
A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk.
2008,
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 Duerr,
The cat-1 gene of Caenorhabditis elegans encodes a vesicular monoamine transporter required for specific monoamine-dependent behaviors.
1999,
Pubmed Etchberger,
Vector-free DNA constructs improve transgene expression in C. elegans.
2008,
Pubmed Fawcett,
Mutant analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in Caenorhabditis elegans.
2006,
Pubmed
,
Xenbase Frøkjaer-Jensen,
Single-copy insertion of transgenes in Caenorhabditis elegans.
2008,
Pubmed Frøkjær-Jensen,
Improved Mos1-mediated transgenesis in C. elegans.
2012,
Pubmed Gendrel,
A secreted complement-control-related protein ensures acetylcholine receptor clustering.
2009,
Pubmed Gómez-Hernández,
Molecular basis of calcium regulation in connexin-32 hemichannels.
2003,
Pubmed
,
Xenbase Jan,
L-glutamate as an excitatory transmitter at the Drosophila larval neuromuscular junction.
1976,
Pubmed Jospin,
The L-type voltage-dependent Ca2+ channel EGL-19 controls body wall muscle function in Caenorhabditis elegans.
2002,
Pubmed Karp,
Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor.
1993,
Pubmed
,
Xenbase Keramidas,
Ligand-gated ion channels: mechanisms underlying ion selectivity.
2004,
Pubmed Khakh,
P2X receptors as cell-surface ATP sensors in health and disease.
2006,
Pubmed Kim,
The dystrophin complex controls bk channel localization and muscle activity in Caenorhabditis elegans.
2009,
Pubmed Krajacic,
Biomechanical profiling of Caenorhabditis elegans motility.
2012,
Pubmed Lambert,
The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.
2010,
Pubmed Liu,
Genetic dissection of ion currents underlying all-or-none action potentials in C. elegans body-wall muscle cells.
2011,
Pubmed Liu,
Gap junctions synchronize action potentials and Ca2+ transients in Caenorhabditis elegans body wall muscle.
2011,
Pubmed Liu,
Low conductance gap junctions mediate specific electrical coupling in body-wall muscle cells of Caenorhabditis elegans.
2006,
Pubmed Lu,
Extracellular calcium controls background current and neuronal excitability via an UNC79-UNC80-NALCN cation channel complex.
2010,
Pubmed Lytton,
Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps.
1991,
Pubmed Ma,
Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca2+ regulation of neuronal excitability.
2012,
Pubmed
,
Xenbase MacDonald,
Paradox of Ca2+ signaling, cell death and stroke.
2006,
Pubmed Maruyama,
2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release.
1997,
Pubmed Mayer,
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones.
,
Pubmed Mello,
Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences.
1991,
Pubmed Minster,
No association between CALHM1 variation and risk of Alzheimer disease.
2009,
Pubmed Morton,
A suite of MATLAB-based computational tools for automated analysis of COPAS Biosort data.
2010,
Pubmed Moyer,
Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations.
2009,
Pubmed Nowak,
Magnesium gates glutamate-activated channels in mouse central neurones.
,
Pubmed Richmond,
One GABA and two acetylcholine receptors function at the C. elegans neuromuscular junction.
1999,
Pubmed Royal,
Temperature-sensitive mutant of the Caenorhabditis elegans neurotoxic MEC-4(d) DEG/ENaC channel identifies a site required for trafficking or surface maintenance.
2005,
Pubmed
,
Xenbase Rusakov,
Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain.
2003,
Pubmed Saez,
Plasma membrane channels formed by connexins: their regulation and functions.
2003,
Pubmed Santi,
Dissection of K+ currents in Caenorhabditis elegans muscle cells by genetics and RNA interference.
2003,
Pubmed Siebert,
Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins.
2013,
Pubmed Smith,
Recordings from single neocortical nerve terminals reveal a nonselective cation channel activated by decreases in extracellular calcium.
2004,
Pubmed Syntichaki,
Specific aspartyl and calpain proteases are required for neurodegeneration in C. elegans.
2002,
Pubmed Sznitman,
Material properties of Caenorhabditis elegans swimming at low Reynolds number.
2010,
Pubmed Taruno,
CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes.
2013,
Pubmed Tong,
Conditions for dye-filling of sensory neurons in Caenorhabditis elegans.
2010,
Pubmed White,
Niflumic and flufenamic acids are potent reversible blockers of Ca2(+)-activated Cl- channels in Xenopus oocytes.
1990,
Pubmed
,
Xenbase Wu,
Transgenic C. elegans as a model in Alzheimer's research.
2005,
Pubmed Xiong,
Extracellular calcium sensed by a novel cation channel in hippocampal neurons.
1997,
Pubmed Xu,
Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.
2001,
Pubmed
,
Xenbase Xu,
Necrotic cell death in C. elegans requires the function of calreticulin and regulators of Ca(2+) release from the endoplasmic reticulum.
2001,
Pubmed Zhang,
Intersubunit interactions between mutant DEG/ENaCs induce synthetic neurotoxicity.
2008,
Pubmed
,
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