Uts2r

Urotensin-2 receptor (UR-2-R) (G protein-coupled receptor 14) (Urotensin II receptor) (UR-II-R)

Spatial tier: RESTRICTED · Class: GPCR · Top region: B (Barrington's nucleus) · Positive regions: 22/554

46.0Discovery Score
36.1Targetability Score
CEvidence grade C
What this means: Uts2r: fine CCF profile is restricted toward B (top regions: B, PCG, AD, LDT, LC; 22 positive regions); direct spatial validation is still required.

Function in B: evidence, prediction, innovation

Gene function
UTS2R (UT, formerly GPR14) is a class A G-protein-coupled receptor for the cyclic peptides urotensin-II and urotensin-related peptide. It couples to Gq, raising intracellular calcium through phospholipase C, and in the periphery mediates one of the most potent vasoconstrictions known. In the central nervous system its expression is strikingly restricted to cholinergic neurons.
Region function
Barrington's nucleus, the pontine micturition centre, contains CRH-positive and glutamatergic neurons projecting to lumbosacral parasympathetic preganglionic neurons; it triggers bladder contraction and coordinates detrusor activity with urethral sphincter relaxation.
Published in this region
inferred No region-specific literature found. Clark et al. 2001 localised UT mRNA to choline acetyltransferase-positive neurons of the rat mesopontine tegmentum, that is the pedunculopontine and laterodorsal tegmental nuclei that immediately abut Barrington's nucleus, and Huitron-Resendiz et al. 2005 showed that urotensin-II applied to these brainstem cholinergic neurons promotes REM sleep; Barrington's nucleus itself was not examined.
Predicted function
Prediction: given that Barrington's CRH and glutamatergic neurons receive strong cholinergic modulation, UT is predicted to sit on or adjacent to these cells and to act as an excitatory Gq modulator that raises bladder-filling sensitivity and lowers the voiding threshold, potentially linking arousal state to continence. Local urotensin-II infusion into Barrington's nucleus should shorten inter-void intervals and reduce threshold bladder volume in cystometry, whereas the antagonist palosuran or urantide should lengthen inter-void intervals; the urotensin-diphtheria-toxin conjugate offers a way to ablate UT-expressing cells and test whether sleep-related voiding control is lost.
Innovation
★★★★★ 5/5 A receptor with well-documented expression in the immediately neighbouring cholinergic tegmentum has never been tested in the pontine micturition centre, a region with clear clinical relevance and excellent Cre tools.
Tools
UT antagonists palosuran, urantide and SB-706375; agonist urotensin-II and URP; urotensin-II-diphtheria toxin conjugate for selective ablation of UT-expressing cholinergic neurons (Clark et al. 2007); Uts2r knockout mice; Crh-Cre and Slc17a6-Cre for Barrington's neuron subtypes.
References

Direct evidence located at the region

Uts2r Allen ISH at the CCF centroid of B

Allen ISH experiment 69288471, section image 69243292 (section 148): the section that contains the CCF centroid of Barrington's nucleus according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Look it up yourself: Allen Mouse Brain ISH for Uts2rAllen reference atlas: B (structure 280)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Uts2r" or by parcellation_substructure "B")All genes confined to B + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
B MERFISH region locator
Real single-cell MERFISH coordinates for the B (Barrington's nucleus) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Uts2r regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

B
0.267
PCG
0.154
AD
0.152
LDT
0.151
LC
0.136
IMD
0.131
SLC
0.123
PN
0.117
SLD
0.116
PVT
0.109
NI
0.101
IF
0.0987
IPDM
0.0978
PG
0.0869
CM
0.0859
IPR
0.0836
VTA
0.0786
AMv
0.0771
PRC
0.0767
MD
0.0765

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.334
Top-region fraction
0.071
Filter status
PASS

Interpretation limits