CNGA2 Membrane Protein Introduction

Introduction of CNGA2

CNGA2 is encoded by the gene CNGA2, which is mapped to the chromosome Xq27. It belongs to the cyclic nucleotide-gated (CNG) ion channels that mediate phototransduction in photoreceptors and chemotransduction in olfactory neurons. Wild-type olfactory CNG channels are heterotetramers composed of two CNGA2 subunits, one CNGA4 subunit, and one CNGB1b subunit, of which only CNGA2 subunits can form functional homotetrameric channels. It was originally believed that CNG channels generate currents through the influx of Na⁺ with the induction of ligand cAMP and cGMP. Afterward, the measurement of permeability ratios between Ca²⁺ and Na⁺ revealed that CNG channels are more permeable to Ca²⁺ than to Na⁺.

Basic Information of CNGA2
Protein Name	Cyclic nucleotide-gated olfactory channel
Gene Name	CNGA2
Aliases	Cyclic nucleotide-gated cation channel 2, Cyclic nucleotide-gated channel alpha-2, CNG channel alpha-2, CNG-2, CNG2, CNCA, CNCA1, CNCG2
Organism	Homo sapiens (Human)
UniProt ID	Q16280
Transmembrane Times	6
Length (aa)	664
Sequence	MTEKTNGVKSSPANNHNHHAPPAIKANGKDDHRTSSRPHSAADDDTSSELQRLADVDAPQQGRSGFRRIVRLVGIIREWANKNFREEEPRPDSFLERFRGPELQTVTTQEGDGKGDKDGEDKGTKKKFELFVLDPAGDWYYCWLFVIAMPVLYNWCLLVARACFSDLQKGYYLVWLVLDYVSDVVYIADLFIRLRTGFLEQGLLVKDTKKLRDNYIHTLQFKLDVASIIPTDLIYFAVDIHSPEVRFNRLLHFARMFEFFDRTETRTNYPNIFRISNLVLYILVIIHWNACIYYAISKSIGFGVDTWVYPNITDPEYGYLAREYIYCLYWSTLTLTTIGETPPPVKDEEYLFVIFDFLIGVLIFATIVGNVGSMISNMNATRAEFQAKIDAVKHYMQFRKVSKGMEAKVIRWFDYLWTNKKTVDEREILKNLPAKLRAEIAINVHLSTLKKVRIFHDCEAGLLVELVLKLRPQVFSPGDYICRKGDIGKEMYIIKEGKLAVVADDGVTQYALLSAGSCFGEISILNIKGSKMGNRRTANIRSLGYSDLFCLSKDDLMEAVTEYPDAKKVLEERGREILMKEGLLDENEVATSMEVDVQEKLGQLETNMETLYTRFGRLLAEYTGAQQKLKQRITVLETKMKQNNEDDYLSDGMNSPELAAADEP

Function of CNGA2 Membrane Protein

Cyclic nucleotide-gated (CNG) channels are a group of Ca²⁺ - permeable channels activated by cAMP and/or cGMP. Among 3 functional CNG isoforms (CNGA1-3), CNGA2 has a higher sensitivity to cAMP than other CNG isoforms. CNGA2 may mediate endothelial Ca²⁺ influx in response to Ca²⁺ store depletion. And CNGA2 mediates endothelial Ca²⁺ influx in response to cAMP and cAMP-elevating agents such as adenosine and β-adrenergic agonists. Because ATP can stimulate cAMP production in vascular endothelial cells, we hypothesize that ATP can also activate CNGA2 in these cells. Olfaction is initiated when odorants bind to their receptors in the olfactory sensory neurons (OSNs), which activate the cAMP signaling pathway and activate a CNG channel. This ion channel is necessary for olfactory sensory neurons to generate odor-induced action potentials which propagate down the axons of OSNs to the olfactory bulb, rendering the essential anosmic in CNGA2 knockout mice.

Fig.1 The phototransduction cascade. (Kramer, 2001)

Application of CNGA2 Membrane Protein in Literature

Xie A.J., et al. Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes. Mol Neurobiol. 2016, 53(7): 4992-4999. PubMed ID: 26377105

This article shows that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins are displayed in CNGA2 knockout mice.
Chen Y., et al. Anxiety- and depressive-like behaviors in olfactory deficient Cnga2 knockout mice. Behav Brain Res. 2014, 275: 219-224. PubMed ID: 25192635

The authors reveal that CNGA2 knockout mice show increased anxiety- and depressive-like behaviors than their wide type siblings.
Nache V., et al. Hysteresis of ligand binding in CNGA2 ion channels. Anim Genet. 2013, 4: 2866. PubMed ID: 24287615

This article suggests that the transition pathways for ligand binding and activation of a fully liganded CNGA2 channel differ from that of ligand unbinding and deactivation, resulting in pronounced hysteresis of the gating mechanism.
Öztokatli H., et al. Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons. FASEB J. 2012, 26(2): 617-627. PubMed ID: 22009938

This article demonstrates a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs.
Kwan H.Y., et al. CNGA2 contributes to ATP-induced noncapacitative Ca²⁺ influx in vascular endothelial cells. J Vasc Res. 2010, 47(2): 148-156. PubMed ID: 19729961

The authors show that CNGA2 channels contribute to ATP-induced non-CCE in vascular endothelial cells. It is likely that ATP acts through P2Y(1)receptors and adenylyl cyclases to stimulate CNGA2.

CNGA2 Preparation Options

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Reference

Kramer R K, et al. (2001). Modulation of cyclic-nucleotide-gated channels and regulation of vertebrate phototransduction. Journal of Experimental Biology. 204, 2921-2931.

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