5-HTR3A Membrane Protein Introduction

Introduction of 5-HTR3A

5-hydroxytryptamine receptor 3A (5-HTR3A), which is alternatively known as 5-hydroxytryptamine receptor 3, is subunit A of the type 3 receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The 5-HTR3A receptor in humans is encoded by the HTR3A gene and belongs to the ligand-gated ion channel receptor superfamily. In the brain, 5-HTR3A is predominantly expressed on interneurons in limbic regions, including hippocampus, cortex, and amygdala.

Basic Information of 5-HTR3A
Protein Name	5-hydroxytryptamine receptor 3A
Gene Name	HTR3A
Aliases	5-hydroxytryptamine receptor 3, Serotonin receptor 3A, Serotonin-gated ion channel receptor, 5-HT3-A, 5-HT3A, 5-HT-3, 5-HT3R
Organism	Homo sapiens (Human)
UniProt ID	P46098
Transmembrane Times	4
Length (aa)	516
Sequence	MLGKLAMLLWVQQALLALLLPTLLAQGEARRSRNTTRPALLRLSDYLLTNYRKGVRPVRDWRKPTTVSIDVIVYAILNVDEKNQVLTTYIWYRQYWTDEFLQWNPEDFDNITKLSIPTDSIWVPDILINEFVDVGKSPNIPYVYIRHQGEVQNYKPLQVVTACSLDIYNFPFDVQNCSLTFTSWLHTIQDINISLWRLPEKVKSDRSVFMNQGEWELLGVLPYFREFSMESSNYYAEMKFYVVIRRRPLFYVVSLLLPSIFLMVMDIVGFYLPPNSGERVSFKITLLLGYSVFLIIVSDTLPATAIGTPLIGKAPPGSRAQSGEKPAPSHLLHVSLASALGCTGVYFVVCMALLVISLAETIFIVRLVHKQDLQQPVPAWLRHLVLERIAWLLCLREQSTSQRPPATSQATKTDDCSAMGNHCSHMGGPQDFEKSPRDRCSPPPPPREASLAVCGLLQELSSIRQFLEKRDEIREVARDWLRVGSVLDKLLFHIYLLAVLAYSITLVMLWSIWQYA

Function of 5-HTR3A Membrane Protein

The 5-HTR3 receptor comprises two subunits, referred to as 5-HTR3A and 5-HTR3B, of which the 5-HTR3A subunit is crucial for the formation of a functional receptor. 5-HTR3A is identified as a ligand-gated ion channel, which upon activation lead to fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel. Especially, the 5-HTR3A protein is the only one that can be expressed alone and forms homomers with a very low single-channel conductance of 0.6pS. 5-HTR3A receptor mediates a rapidly activating, desensitizing, inward current, which is mainly carried by sodium and potassium ions. Several studies have indicated that 5-HTR3 receptor selective compounds may alleviate many diverse potential disease targets, such as pruritis, addiction and neurological phenomena including anxiety, psychosis, nociception, and cognitive function. Since selective pharmacological antagonists have proved to reduce alcohol consumption in preclinical and clinical models, the 5-HTR3 receptor has also become a potential therapeutic target in the treatment of alcohol abuse and alcoholism.

Fig.1 5-HT3 receptor binding sites. (Lummis, 2012)

Application of 5-HTR3A Membrane Protein in Literature

Basak S., et al. Cryo-EM structure of 5-HT3A receptor in its resting conformation. Nat Commun. 2018, 9(1):514. PubMed ID: 29410406

The authors of this study focused on the structure of the full-length 5-HTR3A channel, which was associated with the 5-HTR3A function.
Stratford J.M., et al. 5-HT3A-driven green fluorescent protein delineates gustatory fibers innervating sour-responsive taste cells: A labeled line for sour taste? J Comp Neurol. 2018, 525(10):2358-2375. PubMed ID: 28316078

The results showed that 5-HT3-expressing afferent nerve fibers that projected to a restricted portion of the nTS consistent with a crude mapping of taste quality information in the primary gustatory nucleus.
Ritter K.E., et al. Serotonin Receptor 5-HT3A Affects Development of Bladder Innervation and Urinary Bladder Function. Front Neurosci. 2017, 11:690. PubMed ID: 29311772

The findings of this study highlighted 5-HT3A as a crucial component in the autonomic control of micturition and identified a novel role for 5-HT3A in peripheral nervous system development.
Chen H., et al. Successful treatment with risperidone increases 5-HT3A receptor gene expression in patients with paranoid schizophrenia - data from a prospective study. Brain Behav. 2017, 7(9):e00798. PubMed ID: 28948091

Authors of his study suggested that 5-HT3A receptor might play a role in the mechanism of risperidone effect.
Koyama Y., et al. Building a 5-HT3A Receptor Expression Map in the Mouse Brain. Sci Rep. 2017, 7:42884. PubMed ID: 28276429

The findings of this article were supposed to make a great contribution to elucidating the novel functions of 5-HT3R in the CNS.

5-HTR3A Preparation Options

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Reference

Lummis S C. (2012). 5-HT3 receptors. Journal of Biological Chemistry. 287(48), pp.40239-40245.

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