8s90

Structural highlights

Function

CAHM1_HUMAN Pore-forming subunit of a voltage-gated ion channel required for sensory perception of sweet, bitter and umami tastes (By similarity). Specifically present in type II taste bud cells, where it plays a central role in sweet, bitter and umami taste perception by inducing ATP release from the cell, ATP acting as a neurotransmitter to activate afferent neural gustatory pathways (By similarity). Together with CALHM3, forms a fast-activating voltage-gated ATP-release channel in type II taste bud cells (TBCs) (By similarity). Acts both as a voltage-gated and calcium-activated ion channel: mediates neuronal excitability in response to changes in extracellular Ca(2+) concentration (PubMed:22711817, PubMed:23300080). Has poor ion selectivity and forms a wide pore (around 14 Angstroms) that mediates permeation of Ca(2+), Na(+) and K(+), as well as permeation of monovalent anions (PubMed:22711817). Acts as an activator of the ERK1 and ERK2 cascade (PubMed:23345406). Triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum (PubMed:21574960). May indirectly control amyloid precursor protein (APP) proteolysis and aggregated amyloid-beta (Abeta) peptides levels in a Ca(2+) dependent manner (PubMed:18585350).[UniProtKB:D3Z291]^{[1] [2] [3] [4] [5]}

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. 2008 Jun 27;133(7):1149-61. PMID:18585350 doi:10.1016/j.cell.2008.05.048
2. ↑ Gallego-Sandín S, Alonso MT, García-Sancho J. Calcium homoeostasis modulator 1 (CALHM1) reduces the calcium content of the endoplasmic reticulum (ER) and triggers ER stress. Biochem J. 2011 Aug 1;437(3):469-75. PMID:21574960 doi:10.1042/BJ20110479
3. ↑ 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. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):E1963-71. PMID:22711817 doi:10.1073/pnas.1204023109
4. ↑ Siebert AP, Ma Z, Grevet JD, Demuro A, Parker I, Foskett JK. Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. J Biol Chem. 2013 Mar 1;288(9):6140-53. PMID:23300080 doi:10.1074/jbc.M112.409789
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. 2013 Mar 1;126(Pt 5):1199-206. PMID:23345406 doi:10.1242/jcs.117135