CALHM1 Membrane Protein Introduction

Introduction of CALHM1

CALHM1 (calcium homeostasis regulator 1) is a cell surface calcium channel expressed in brain neurons that controls intracellular calcium signaling and cell excitability, the two mechanisms required for synaptic function. CALHM1 forms a plasma membrane ion channel that mediates neuronal excitability in response to changes in extracellular Ca²⁺ concentration. The CALHM1 channel is a hexamer consisting of six monomers, each having four transmembrane domains, a cytoplasmic amino and carboxy terminus, an amino-terminal helix, and a conserved extracellular cysteine. The CALHM1 channel has an estimated pore size of ~14Å and is capable of penetrating large charged molecules.

Function of CALHM1 Membrane Protein

CALHM1 is a pore-forming subunit of voltage-gated ion channels for the perception of sweetness, bitterness and umami taste, especially in type II taste bud cells, which are sweet, bitter and fresh by inducing ATP release from cells. It acts as a voltage-gated and calcium-activated ion channel: it responds to changes in extracellular Ca²⁺ concentration that mediates neuronal excitability. It also mediates the penetration of Ca²⁺, Na⁺, and K⁺, as well as the penetration of monovalent anions, and acts as an activator of the ERK1 and ERK2 cascades, which triggers endoplasmic reticulum stress by reducing the calcium content of the endoplasmic reticulum.

Fig.1 Proposed signaling pathway in type II receptor cells. (Shigeyuki, 2017)

Application of CALHM1 Membrane Protein in Literature

1. Moreno-Ortega A.J., et al. CALHM1 and its polymorphism P86L differentially control Ca²⁺ homeostasis, mitogen-activated protein kinase signaling, and cell vulnerability upon exposure to amyloid β. Aging Cell. 2015, 14(6): 1094-1102. PubMed ID: 26416646
   
   

   This article reports that the mutated form of Ca²⁺ channel CALHM1 (Ca²⁺ homeostasis regulator 1), P86L-CALHM1, is related to the early onset of Alzheimer's disease (AD).

2. Vingtdeux V., et al. CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice. Scientific Reports. 2016, 6: 24250. PubMed ID: 27066908
   
   

   This article reveals that activation of CALHM1 promotes phosphorylation of NMDA and AMPA receptors by protein kinase A, and activation of neuronal CALHM1 enhances the effects of glutamate on c-Fos and C/EBPβ expression, two immediate-early gene marker of neuronal activity. CALHM1 controls synaptic activity in brain neurons and is involved in the flexible processing of mouse memory.

3. Siebert A.P., et al. Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. J Biol Chem. 2013, 288(9): 6140-6153, PubMed ID: 23300080
   
   

   This article indicates that CALHM1 is involved in the formation of plasma membrane ion channels, which are sensitive to changes in extracellular Ca²⁺ concentration, thereby mediating neuronal excitability.

4. Ma Z., et al. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells. J Neurophysiol. 2017, 117(5): 1865-1876. PubMed ID: 28202574
   
   

   This article shows that CALHM1 is an essential ion channel component of ATP neurotransmitter release mechanism in type II taste bud cells. Type II taste bud cells stimulate action potentials in response to tastants and trigger non-cystic ATP release to taste neurons via voltage-gated CALHM1-related ion channels.

5. Vingtdeux V., et al. CALHM1 ion channel elicits amyloid-β clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain. J Cell Sci. 2015, 128(13): 2330-2338, PubMed ID: 25999473
   
   

   This article evaluates that CALHM1 promotes neuronal and Ca²⁺-dependent degradation of extracellular Aβ by insulin degrading enzymes (IDE) to control Aβ levels in cell lines and in vivo. Therefore, we can use the CALHM1 ion channel as a potential target for promoting amyloid clearance in AD.

CALHM1 Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CALHM1 antibody development services.

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Reference

1. Matsui S and Takahashi H (2017). Is egg flavour changeable by chicken breeding? Association of chicken fatty acid desaturase 1 gene single-nucleotide polymorphisms with egg fatty acid profiles and flavour in a Japanese hybrid chicken. Cogent Food & Agriculture. 3(1): 1287812.

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