RRC ID 46210
著者 Tanis JE, Ma Z, Krajacic P, He L, Foskett JK, Lamitina T.
タイトル CLHM-1 is a functionally conserved and conditionally toxic Ca2+-permeable ion channel in Caenorhabditis elegans.
ジャーナル J Neurosci
Abstract 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.
巻・号 33(30)
ページ 12275-86
公開日 2013-7-24
DOI 10.1523/JNEUROSCI.5919-12.2013
PII 33/30/12275
PMID 23884934
PMC PMC3721838
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Calcium Channel Blockers / pharmacology Calcium Channels / genetics* Calcium Channels / metabolism* Cell Membrane / physiology Electric Stimulation Humans Locomotion / genetics Locomotion / physiology Membrane Glycoproteins / genetics* Membrane Glycoproteins / metabolism* Membrane Potentials / physiology Nerve Degeneration / pathology Nerve Degeneration / physiopathology Oocytes / cytology Sensory Receptor Cells / pathology Sensory Receptor Cells / physiology Species Specificity Touch / physiology Transgenes / genetics Xenopus laevis
IF 5.674
引用数 18
WOS 分野 NEUROSCIENCES
リソース情報
線虫 tm4071