Prokr2

Prokineticin receptor 2 (PK-R2) (G protein-coupled receptor 73-like 1)

Spatial tier: RESTRICTED · Class: GPCR · Top region: AP (Area postrema) · Positive regions: 15/554

46.2Discovery Score
43.5Targetability Score
CEvidence grade C
What this means: Prokr2: fine CCF profile is restricted toward AP (top regions: AP, SCH, PVT, TMd, PMd; 15 positive regions); direct spatial validation is still required.

Function in AP: evidence, prediction, innovation

Gene function
PROKR2 (PKR2) is a class A G-protein-coupled receptor for the secreted peptide prokineticin-2. It couples mainly to Gq, raising intracellular calcium, and also to Gi. Prokineticin-2 is a major diffusible output signal of the suprachiasmatic clock, and PROKR2 additionally guides olfactory bulb morphogenesis and GnRH neuron migration; loss-of-function mutations in humans cause Kallmann syndrome with hypogonadotropic hypogonadism.
Region function
The area postrema is a circumventricular organ on the floor of the fourth ventricle with fenestrated capillaries and no blood-brain barrier; it samples circulating toxins, hormones and peptides and drives nausea, conditioned taste avoidance and suppression of feeding through the NTS and parabrachial nucleus.
Published in this region
expression only Expression is well documented, function is not. Cheng et al. 2006 found prominent Prokr2 mRNA in circumventricular organs including the area postrema in their in situ survey of adult mouse brain, and Mohsen et al. 2017, using a Prokr2-Cre reporter, confirmed a high density of labelled cells in the subfornical organ, subcommissural organ and area postrema. No study has manipulated PROKR2 within the area postrema.
Predicted function
Prediction: AP PROKR2 neurons are well placed to let the circadian prokineticin-2 signal, and prokineticin arriving from the circulation, gate the sensitivity of the nausea and satiety pathway across the day. Chemogenetic activation of AP Prokr2-Cre neurons should suppress food intake and induce conditioned taste avoidance with Fos in NTS and parabrachial nucleus; conditional deletion of Prokr2 in AP should flatten the circadian variation in emetic and anorectic responses to peripheral challenges while leaving circadian locomotor rhythm intact.
Innovation
★★★★☆ 4/5 A Cre line already labels these AP cells and expression is documented, yet nobody has asked what PROKR2 signalling does in this nucleus.
Tools
Prokr2-Cre (Mohsen et al. 2017) and Prokr2-null mice; prokineticin-2 peptide; PKR antagonists PC-7 and PKRA7; anti-PROKR2 antibodies. AP is reachable by fourth-ventricle or direct stereotaxic AAV.
References

Direct evidence located at the region

Prokr2 Allen ISH at the CCF centroid of AP

Allen ISH experiment 74511780, section image 74395980 (section 50): the section that contains the CCF centroid of Area postrema 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

Direct spatial evidence

MERFISH REGION LOCATOR
AP MERFISH region locator
Real single-cell MERFISH coordinates for the AP (Area postrema) 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

Prokr2 regional expression profile

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

Spatial profile

AP
4.74
SCH
3.33
PVT
2.84
TMd
2.48
PMd
1.74
MMm
1.68
LSc
1.55
SBPV
1.46
PVp
1.45
PT
1.33
LH
1.33
AOBgr
1.2
MMme
1.17
MMp
1.16
MMl
1.13
CA2sp
1.04
SH
1.03
PA
1
PVa
0.931
CM
0.823

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.354
Top-region fraction
0.093
Filter status
PASS

Interpretation limits