CALHM1

Last updated
CALHM1
Identifiers
Aliases CALHM1 , FAM26C, calcium homeostasis modulator 1
External IDs OMIM: 612234 MGI: 3643383 HomoloGene: 55508 GeneCards: CALHM1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001001412

NM_001081271

RefSeq (protein)

NP_001001412

NP_001074740

Location (UCSC) Chr 10: 103.45 – 103.46 Mb Chr 19: 47.13 – 47.13 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6]

Contents

Function

Central nervous system

CALHM1 was identified by a tissue-specific gene expression profiling approach [7] that screened for genes located on susceptibility loci for late-onset Alzheimer's disease (AD) and that are preferentially expressed in the hippocampus, [5] a brain region affected early in AD. CALHM1 is a plasma membrane calcium-permeable ion channel regulated by voltage and extracellular calcium levels. [8] 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. [8] [9] [10] Recent data have also shown that CALHM1 might facilitate the proteolytic degradation of the cerebral amyloid beta peptide, a culprit in AD pathogenesis. [11]

Peripheral taste system

CALHM1 is expressed in taste bud cells where it controls purinergic receptor-mediated taste transduction in the gustatory system. [12] [13]

See also

Related Research Articles

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<span class="mw-page-title-main">Sweetness</span> Basic taste

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The P-type calcium channel is a type of voltage-dependent calcium channel. Similar to many other high-voltage-gated calcium channels, the α1 subunit determines most of the channel's properties. The 'P' signifies cerebellar Purkinje cells, referring to the channel's initial site of discovery. P-type calcium channels play a similar role to the N-type calcium channel in neurotransmitter release at the presynaptic terminal and in neuronal integration in many neuronal types.

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<span class="mw-page-title-main">CACNB3</span>

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<span class="mw-page-title-main">CACNA2D1</span>

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<span class="mw-page-title-main">KCNN1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">KCNMB4</span>

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<span class="mw-page-title-main">Calcium channel, voltage-dependent, T type, alpha 1H subunit</span>

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<span class="mw-page-title-main">Acid-sensing ion channel</span> Class of transport proteins

Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels activated by extracellular protons permeable to Na+. ASIC1 also shows low Ca2+ permeability. ASIC proteins are a subfamily of the ENaC/Deg superfamily of ion channels. These genes have splice variants that encode for several isoforms that are marked by a suffix. In mammals, acid-sensing ion channels (ASIC) are encoded by five genes that produce ASIC protein subunits: ASIC1, ASIC2, ASIC3, ASIC4, and ASIC5. Three of these protein subunits assemble to form the ASIC, which can combine into both homotrimeric and heterotrimeric channels typically found in both the central nervous system and peripheral nervous system. However, the most common ASICs are ASIC1a and ASIC1a/2a and ASIC3. ASIC2b is non-functional on its own but modulates channel activity when participating in heteromultimers and ASIC4 has no known function. On a broad scale, ASICs are potential drug targets due to their involvement in pathological states such as retinal damage, seizures, and ischemic brain injury.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185933 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000079258 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 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 (Jun 2008). "A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk". Cell. 133 (7): 1149–61. doi:10.1016/j.cell.2008.05.048. PMC   2577842 . PMID   18585350.
  6. Taruno A, Matsumoto I, Ma Z, Marambaud P, Foskett JK (December 2013). "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. doi:10.1002/bies.201300077. PMC   3981604 . PMID   24105910.
  7. Skrabanek L, Campagne F (Nov 2001). "TissueInfo: high-throughput identification of tissue expression profiles and specificity". Nucleic Acids Research. 29 (21): E102-2. doi:10.1093/nar/29.21.e102. PMC   60201 . PMID   11691939.
  8. 1 2 Ma Z, Siebert AP, Cheung KH, Lee RJ, Johnson B, Cohen AS, Vingtdeux V, Marambaud P, Foskett JK (Jul 2012). "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. Bibcode:2012PNAS..109E1963M. doi: 10.1073/pnas.1204023109 . PMC   3396471 . PMID   22711817.
  9. Dreses-Werringloer U, Vingtdeux V, Zhao H, Chandakkar P, Davies P, Marambaud P (Mar 2013). "CALHM1 controls the Ca²⁺-dependent MEK, ERK, RSK and MSK signaling cascade in neurons". J Cell Sci. 126 (Pt 5): 1199–206. doi:10.1242/jcs.117135. PMC   4481642 . PMID   23345406.
  10. Vingtdeux V, Chang EH, Frattini SA, Zhao H, Chandakkar P, Adrien L, Strohl JJ, Gibson EL, Ohmoto M, Matsumoto I, Huerta PT, Marambaud P (Apr 2016). "CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice". Sci Rep. 6 (24250): 24250. Bibcode:2016NatSR...624250V. doi:10.1038/srep24250. PMC   4828655 . PMID   27066908.
  11. Vingtdeux V, Chandakkar P, Zhao H, Blanc L, Ruiz S, Marambaud P (May 2015). "CALHM1 ion channel elicits amyloid-β clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain". J Cell Sci. 128 (13): 2330–8. doi:10.1242/jcs.167270. PMC   4524106 . PMID   25999473.
  12. 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 (Mar 2013). "CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes". Nature. 495 (7440): 223–6. Bibcode:2013Natur.495..223T. doi:10.1038/nature11906. PMC   3600154 . PMID   23467090.
  13. Kinnamon SC, Finger TE (Dec 2013). "A taste for ATP: neurotransmission in taste buds". Front Cell Neurosci. 7: 264. doi: 10.3389/fncel.2013.00264 . PMC   3866518 . PMID   24385952.

Further reading