CALHM1 explained

Calcium homeostasis modulator 1 (CALHM1) is a pore-forming subunit of a voltage-gated ion channel and a voltage-gated ATP channel that in humans is encoded by the CALHM1 gene.^{[1] [2]}

Function

Central nervous system

CALHM1 was identified by a tissue-specific gene expression profiling approach^[3] that screened for genes located on susceptibility loci for late-onset Alzheimer's disease (AD) and that are preferentially expressed in the hippocampus,^[1] a brain region affected early in AD. CALHM1 is a plasma membrane calcium-permeable ion channel regulated by voltage and extracellular calcium levels.^[4] The exact function of CALHM1 in the brain is not completely understood, but studies have shown that CALHM1 controls neuronal intracellular calcium homeostasis and signaling, as well as calcium-dependent neuronal excitability and memory in mouse models.^{[4] [5] [6]} Recent data have also shown that CALHM1 might facilitate the proteolytic degradation of the cerebral amyloid beta peptide, a culprit in AD pathogenesis.^[7]

Peripheral taste system

CALHM1 is expressed in taste bud cells where it controls purinergic receptor-mediated taste transduction in the gustatory system.^{[8] [9]}

See also

• Ruthenium red

Further reading

• Moyer BD, Hevezi P, Gao N, Lu M, Kalabat D, Soto H, Echeverri F, Laita B, Yeh SA, Zoller M, Zlotnik A . Expression of genes encoding multi-transmembrane proteins in specific primate taste cell populations . PLOS ONE . 4 . 12 . e7682 . Dec 2009 . 19997627 . 10.1371/journal.pone.0007682 . 2780358. 2009PLoSO...4.7682M . free .
• Moreno-Ortega AJ, Ruiz-Nuño A, García AG, Cano-Abad MF . Mitochondria sense with different kinetics the calcium entering into HeLa cells through calcium channels CALHM1 and mutated P86L-CALHM1 . Biochemical and Biophysical Research Communications . 391 . 1 . 722–6 . Jan 2010 . 19944073 . 10.1016/j.bbrc.2009.11.127 .
• Desharnais R, Godin G, Jobin J, Valois P, Ross A . Optimism and health-relevant cognitions after a myocardial infarction . Psychological Reports . 67 . 3 Pt 2 . 1131–1135 . Dec 1990 . 2084739 . 10.2466/pr0.1990.67.3f.1131 . 46335269 .
• Lv RJ, He JS, Fu YH, Shao XQ, Wu LW, Lu Q, Jin LR, Liu H . A polymorphism in CALHM1 is associated with temporal lobe epilepsy . Epilepsy & Behavior . 20 . 4 . 681–5 . Apr 2011 . 21439911 . 10.1016/j.yebeh.2011.02.007. 45287698 .

Notes and References

1. Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H, Siebert A, Jain A, Koppel J, Rovelet-Lecrux A, Hannequin D, Pasquier F, Galimberti D, Scarpini E, Mann D, Lendon C, Campion D, Amouyel P, Davies P, Foskett JK, Campagne F, Marambaud P . A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk . Cell . 133 . 7 . 1149–61 . Jun 2008 . 18585350 . 10.1016/j.cell.2008.05.048 . 2577842.
2. Taruno A, Matsumoto I, Ma Z, Marambaud P, Foskett JK . How do taste cells lacking synapses mediate neurotransmission? CALHM1, a voltage-gated ATP channel . BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology . 35 . 12 . 1111–8 . December 2013 . 24105910 . 3981604 . 10.1002/bies.201300077 .
3. Skrabanek L, Campagne F . TissueInfo: high-throughput identification of tissue expression profiles and specificity . Nucleic Acids Research . 29 . 21 . E102-2 . Nov 2001 . 11691939 . 10.1093/nar/29.21.e102 . 60201.
4. Ma Z, Siebert AP, Cheung KH, Lee RJ, Johnson B, Cohen AS, Vingtdeux V, Marambaud P, Foskett JK . Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca2+ regulation of neuronal excitability . Proceedings of the National Academy of Sciences of the United States of America . 109 . 28 . E1963-71 . Jul 2012 . 22711817 . 10.1073/pnas.1204023109 . 3396471. 2012PNAS..109E1963M . free .
5. Dreses-Werringloer U, Vingtdeux V, Zhao H, Chandakkar P, Davies P, Marambaud P . CALHM1 controls the Ca²⁺-dependent MEK, ERK, RSK and MSK signaling cascade in neurons . J Cell Sci . 126 . 1199–206 . Mar 2013 . Pt 5 . 23345406 . 10.1242/jcs.117135 . 4481642.
6. Vingtdeux V, Chang EH, Frattini SA, Zhao H, Chandakkar P, Adrien L, Strohl JJ, Gibson EL, Ohmoto M, Matsumoto I, Huerta PT, Marambaud P . CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice . Sci Rep . 6 . 24250 . Apr 2016 . 27066908 . 10.1038/srep24250 . 4828655 . 24250. 2016NatSR...624250V .
7. Vingtdeux V, Chandakkar P, Zhao H, Blanc L, Ruiz S, Marambaud P . CALHM1 ion channel elicits amyloid-β clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain . J Cell Sci . May 2015 . 25999473 . 10.1242/jcs.167270 . 128 . 13 . 2330–8 . 4524106.
8. Taruno A, Vingtdeux V, Ohmoto M, Ma Z, Dvoryanchikov G, Li A, Adrien L, Zhao H, Leung S, Abernethy M, Koppel J, Davies P, Civan MM, Chaudhari N, Matsumoto I, Hellekant G, Tordoff MG, Marambaud P, Foskett JK . CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes . Nature . 495 . 7440 . 223–6 . Mar 2013 . 23467090 . 10.1038/nature11906 . 3600154. 2013Natur.495..223T .
9. Kinnamon SC, Finger TE . A taste for ATP: neurotransmission in taste buds . Front Cell Neurosci . 7 . 264 . Dec 2013 . 24385952 . 10.3389/fncel.2013.00264 . 3866518. free .