CHRNA9 Membrane Protein Introduction

Introduction of CHRNA9

CHRNA9, a gene encoding the neuronal acetylcholine receptor subunit alpha-9, is localized to chromosome 4p14 and contains five exons, separated by four introns. Exons 1-5 are 78, 145,154, 532 and 877 bases, respectively. CHRNA9 protein is a plasma membrane protein of divalent cation channels and is found in human epidermal keratinocytes. To date, these particular receptors are found predominantly in the inner ear and specifically on the surface of type II hair cells. CHRNA9 connected with CHRNA10 form homo- or heterooligomeric channels. The native outer hair cell receptor may be composed of CHRNA9-CHRNA10 heterooligomers.

Function of CHRNA9 Membrane Protein

Neuronal acetylcholine receptor subunit alpha-9 may play a role in the modulation of auditory stimuli. Conformation resulting from change agonist binding induces a leads to the opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium. The divalent cations influx may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may also protect against acoustic trauma and regulate keratinocyte adhesion. Additionally, previous studies have demonstrated overexpression and activation of CHRNA9 protein during human breast epithelial cell tumorigenesis, while inhibition of CHRNA9 protein signaling shows antitumor effects on human breast cancer cells.

Fig.1 Schematic summary of the (phospho-) cholinergic inhibition of ATP-induced inflammasome activation in monocytes. Endogenous ligands of CHRNA7, CHRNA9, and/or CHRNA10, such as ACh, choline, or PC, inhibit ATP-dependent release of IL-1β (Hecker, 2015)

Application of CHRNA9 Membrane Protein in Literature

1. Mohammadi S.A., et al. α9-nAChR knockout mice exhibit dysregulation of stress responses, affect and reward-related behaviour. Behavior Brain Research. 2017, 328:105-114. PubMed ID: 28408300
   
   

   This article uncovers a novel role for the α9α10-nAChR in mounting a normal stress response and in the regulation of affective- and reward-related behaviour, and suggests that pursuing the receptor for clinical treatments may not be as straightforward as has been suggested.

2. Tu L., et al. Alpha-9 nicotinic acetylcholine receptors mediate hypothermic responses elicited by provocative motion in mice. Physiology Behav. 2017, 174:114-119. PubMed ID: 28302571
   
   

   This article confirms that hypothermia is a biological correlate of a nausea-like state in animals using knockout (KO) mice lacking alpha-9 nicotinic acetylcholine receptors as a wild-type (WT) control.

3. Wang Y., et al. Neuronal acetylcholine receptor subunit alpha-9 (CHRNA9) polymorphisms are associated with NSCLC risk in a Chinese population. Medecine Oncology. 2014, 31(5):932. PubMed ID: 24676996
   
   

   The CHRNA9 rs6819385 SNP was significantly related to an increased risk of NSCLC in Chinese population.

4. Hsieh Y.C., et al. CHRNA9 polymorphisms and smoking exposure synergize to increase the risk of breast cancer in Taiwan. Carcinogenesis. 2014, 35(11):2520-5. PubMed ID: 25142973
   
   

   This article supports that CHRNA9 gene and smoking exposure have correlation on the risk of breast cancer development.

5. Huang L.C., et al. Nicotinic acetylcholine receptor subtype alpha-9 mediates triple-negative breast cancers based on a spontaneous pulmonary metastasis mouse model. Front Cell Neurosci. 2017, 11:336. PubMed ID: 29163048
   
   

   This article reveals that α9-nAChR expression is important to mediate TNBC metastasis during cancer development and may potentially function as a biomarker for targeted therapy in clinical investigations.

CHRNA9 preparation options

Membrane protein studies have developed greatly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CHRNA9 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Hecker A, et al. (2015). Phosphocholine-modified macromolecules and canonical nicotinic agonists inhibit ATP-induced IL-1β release. J Immunol. 195(5), 2325-34.

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