Gpr55

G protein-coupled receptor 55

Spatial tier: STRICT_EXCLUSIVE · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 7/554

44.8Discovery Score
36.4Targetability Score
CEvidence grade C
What this means: Gpr55: predicted fine-region profile is strict-exclusive, with 7 positive regions out of 554 (limit 12); direct spatial validation is required.

Function in SCO: evidence, prediction, innovation

Gene function
Gpr55 encodes an orphan-derived class-A GPCR activated by L-alpha-lysophosphatidylinositol (LPI) and, with debate, by THC, anandamide and O-1602; cannabidiol is an antagonist. It couples to G12/13-RhoA-ROCK and Gq, giving Ca2+ release, ERK activation and cytoskeletal contraction, and is structurally distinct from CB1/CB2.
Region function
The subcommissural organ is a secretory ependymal gland under the posterior commissure at the third-ventricle/aqueduct junction, releasing SCO-spondin into CSF to form Reissner's fibre and shaping aqueduct patency, CSF flow and axial morphogenesis.
Published in this region
inferred No region-specific literature found. Closest: GPR55 modulates pain in the adjacent periaqueductal grey (Deliu et al. 2015) and hippocampal synaptic plasticity (Hurst et al. 2017), while the related lysophospholipid LPA acting on CSF-facing cells initiates fetal and post-haemorrhagic hydrocephalus (Yung et al. 2011).
Predicted function
Prediction: GPR55 lets SCO cells read CSF lysophospholipid tone, LPI acting through G12/13-RhoA-ROCK on apical actomyosin tension, junctional integrity and granule release, the axis by which LPA injures ventricular surfaces. Gpr55 knockout or CID16020046 should preserve Reissner's fibre and aqueduct patency in LPA- or blood-induced hydrocephalus; LPI or O-1602 should disrupt SCO-spondin release and cause ventriculomegaly.
Innovation
★★★★★ 5/5 GPR55 has never been examined in any ventricular secretory epithelium, yet lysophospholipid signalling is a validated hydrocephalus mechanism.
Tools
Gpr55 knockout mice (Gpr55tm1Lex, Lexicon/Deltagen); agonists LPI, O-1602, ML184; antagonists CID16020046, ML193, cannabidiol; Sspo-Cre/Sspo-CreER; antibodies are poor, so use RNAscope.
References

Direct evidence located at the region

Gpr55 Allen ISH at the CCF centroid of SCO

Allen ISH experiment 79591399, section image 79603813 (section 236): the section that contains the CCF centroid of Subcommissural organ 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
SCO MERFISH region locator
Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.
DIRECT ALLEN ISH
Allen ISH experiment 79591399, image 79603741 -- target region: SCO (Subcommissural organ)
Allen ISH experiment 79591399, image 79603741 -- target region: SCO (Subcommissural organ)
DIRECT ALLEN ISH
Allen ISH experiment 79591399, image 79603743 -- target region: SCO (Subcommissural organ)
Allen ISH experiment 79591399, image 79603743 -- target region: SCO (Subcommissural organ)

Regional expression figure

Gpr55 regional expression profile

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

Spatial profile

SCO
0.391
PVpo
0.246
MH
0.179
PVi
0.167
OT
0.165
ACB
0.149
PVa
0.129
CEAc
0.112
NLOT2
0.108
AVPV
0.107
OV
0.104
PVH
0.101
CEAl
0.101
SFO
0.0989
MPN
0.0969
LA
0.0965
IA
0.0965
MEPO
0.0945
CP
0.0944
AIp6b
0.0932

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.320
Top-region fraction
0.098
Filter status
PASS

Interpretation limits