Cmklr1

Chemerin-like receptor 1 (Chemokine-like receptor 1) (G protein-coupled receptor DEZ)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: ME (Median eminence) · Positive regions: 44/554

43.7Discovery Score
36.3Targetability Score
CEvidence grade C
What this means: Cmklr1: fine CCF profile is region-biased toward ME (top regions: ME, AId1, MMd, AUDd1, SSp-m1); this is a discovery lead, not direct proof.

Function in ME: evidence, prediction, innovation

Gene function
Cmklr1 (ChemR23) encodes a Gi/o-coupled chemoattractant GPCR whose main agonist is the adipokine chemerin after C-terminal proteolytic activation; resolvin E1 is also reported to act at it. Signalling lowers cAMP, mobilises calcium and recruits beta-arrestin2, driving leukocyte chemotaxis, adipogenesis and glucose handling.
Region function
The median eminence is a circumventricular organ where hypophysiotropic terminals release hormones into fenestrated portal capillaries, and whose tanycytes and ependymal cells sense circulating metabolic signals and remodel seasonally.
Published in this region
direct Helfer 2016 identified chemerin as a retinoic-acid target in photoperiodic F344 rats and localised chemerin and its receptors, including CMKLR1, to tanycytes and ependymal cells of the hypothalamic ventricular zone and median eminence, higher under long than short photoperiod; chronic ICV chemerin mimicked the long-day rise in food intake and raised vimentin, implicating tanycyte remodelling. Yun 2022 showed arcuate CMKLR1 knockdown and alpha-NETA alter body weight. Allen ISH gives ME 0.35-0.53 versus 0.17 for grey matter (experiment 72340129).
Predicted function
Prediction: tanycytic rather than neuronal CMKLR1 is the median eminence receptor for circulating chemerin, converting adiposity signals into cytoskeletal remodelling that changes barrier permeability and terminal access to portal blood. Tanycyte-restricted deletion or local alpha-NETA should abolish photoperiodic and diet-driven remodelling, blunt seasonal weight cycling and reduce hyperphagia after a switch to long photoperiod.
Innovation
★★★☆☆ 3/5 Tanycyte localisation and ICV pharmacology exist in rat, but no cell-type-specific genetic test in the median eminence has been reported.
Tools
Cmklr1 knockout mice (Ernst 2012); selective antagonist alpha-NETA (Graham 2014); chemerin-9; validated anti-CMKLR1 shRNA lentivirus for stereotaxic knockdown (Yun 2022); IUPHAR-curated chemerin receptor ligands (Kennedy 2018).
References

Direct evidence located at the region

Cmklr1 Allen ISH at the CCF centroid of ME

Allen ISH experiment 72340129, section image 72162799 (section 249): the section that contains the CCF centroid of Median eminence 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
ME MERFISH region locator
Real single-cell MERFISH coordinates for the ME (Median eminence) 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

Cmklr1 regional expression profile

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

Spatial profile

ME
0.577
AId1
0.36
MMd
0.346
AUDd1
0.345
SSp-m1
0.341
SSs1
0.323
TEa1
0.317
IG
0.314
AUDpo1
0.308
AUDv1
0.306
VISl1
0.294
SSp-ul1
0.294
MOp1
0.293
SSp-n1
0.29
GU1
0.289
VISC1
0.288
MOs1
0.285
VISam1
0.28
ECT1
0.28
VISli1
0.278

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.294
Top-region fraction
0.049
Filter status
PASS

Interpretation limits