TACR1 gene

The TACR1 gene (TACR1 stands for: Tachykinin Receptor 1) is a protein-coding gene located on chromosome 2p12. The TACR1 gene encodes the receptor of the same name (TCAR1 or NK1 receptor) whose ligand is tachykinin, also known as "substance P" or neurokinin 1. The encoded receptor protein is also involved in the regulation of the phosphatidylinositol metabolism of substance P. Tachykinin receptors are characterized by interactions with G proteins and (like other transmembrane receptors) have seven hydrophobic transmembrane regions.

TACR1, as a receptor for "substance P", is probably associated with G-proteins that activate a phosphatidylinositol calcium second messenger system. TCAR1 (NK1 receptor) belongs to the tachykinin family, a group of G-protein-coupled receptors that also includes the NK2 and NK3 receptors. The NK1 receptor is found in high concentrations in the central nervous system (particularly in the striatum and amygdala) and in peripheral tissues.

Diseases associated with TACR1 include cystitis and fibromyalgia . Associated signaling pathways include class A/1 (rhodopsin-like receptors) and downstream G protein-coupled receptor (GPCR ) signaling.

Activation of a subset of spinal cord neurons expressing Tacr1 elicits a full repertoire of somatotopically directed pain-related behaviors in the absence of noxious stimuli. Thus, Tacr1 projection neurons (expressing NKR1) target a tiny group of neurons in the superior lateral parabrachial nucleus (Barik A et al. 2012). TACR1 with its ligand Nk1 also plays an important role in itching (Piyush Shah D et al. 2022). However, it is still unclear how exposure to a pruritogen is translated into the perception of itch and how this perception triggers scratching at the site of exposure.

The affinity of the receptor to tachykinins decreases in the following order: substance P > substance K > neuromedin-K. The Gene Ontology (GO) describes the activity of G protein-coupled receptors and substance P receptors. An important paralog of this gene is TACR3 .

1. Barik A et al. (2012) A spinoparabrachial circuit defined by Tacr1 expression drives pain. Elife 10:e61135.
2. Piyush Shah D et al. (2022) The Spino-Parabrachial Pathway for Itch. Front Neural Circuits 16:805831.