Slc22a22

Solute carrier family 22 member 22 (Prostaglandin-specific organic anion transporter)

Spatial tier: RESTRICTED · Class: GPCR · Top region: SUM (Supramammillary nucleus) · Positive regions: 13/554

45.3Discovery Score
35.1Targetability Score
CEvidence grade C
What this means: Slc22a22: fine CCF profile is restricted toward SUM (top regions: SUM, MMme, MMl, ILA2/3, MMd; 13 positive regions); direct spatial validation is still required.

Function in SUM: evidence, prediction, innovation

Gene function
Slc22a22 encodes OAT-PG, an organic anion transporter of the SLC22 family that selectively takes up prostaglandin E2. It was cloned from kidney, where it clears PGE2 from the cortical interstitium; its expression is regulated by glucocorticoids and by sex hormones. Despite being grouped with GPCR-like annotations, it is a transporter, not a receptor.
Region function
The supramammillary nucleus is a small posterior hypothalamic cell group projecting heavily to medial septum, dentate gyrus and CA2; it signals novelty and arousal and sets hippocampal theta rhythm and wakefulness.
Published in this region
inferred No region-specific literature found. All published OAT-PG work is renal: glucocorticoid control of its transcription (Hatano 2014), a sex difference in renal expression that sets basal PGE2 (Hatano 2012), and reduced expression during pregnancy (Kazama 2013). No brain expression or function has been reported for Slc22a22, while the supramammillary nucleus itself is well defined as a glutamatergic arousal node (Pedersen 2017).
Predicted function
Prediction: if supramammillary neurons really express OAT-PG they would be able to take up and clear extracellular PGE2, giving this novelty-and-arousal node a direct handle on prostaglandin signalling during fever and inflammation. That predicts inflammatory states raise local PGE2 in SUM and thereby modulate hippocampal theta and novelty responses, and that Slc22a22 deletion or a prostaglandin-transport blocker would exaggerate PGE2-driven changes in arousal and theta power. Because this is otherwise a kidney gene, expression validation must come first.
Innovation
★★★★★ 5/5 Prostaglandin uptake by an arousal nucleus is an entirely unexplored idea, though the complete absence of gene-specific reagents raises the cost of testing it.
Tools
None known for Slc22a22 itself: no knockout, Cre line or validated antibody in common use. Prostaglandin transport can be probed pharmacologically with bromosulfophthalein, probenecid and indomethacin; supramammillary neurons are accessible with Vglut2-IRES-Cre (JAX 028863) and by retro-AAV from dentate gyrus or medial septum.
References

Direct evidence located at the region

Slc22a22 Allen ISH at the CCF centroid of SUM

Allen ISH experiment 69261398, section image 69205358 (section 138): the section that contains the CCF centroid of Supramammillary 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

Direct spatial evidence

MERFISH REGION LOCATOR
SUM MERFISH region locator
Real single-cell MERFISH coordinates for the SUM (Supramammillary 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

Slc22a22 regional expression profile

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

Spatial profile

SUM
0.167
MMme
0.0946
MMl
0.0838
ILA2/3
0.0736
MMd
0.0708
GU2/3
0.0652
AIp2/3
0.0633
PERI2/3
0.0607
AId2/3
0.0598
B
0.0589
VISC2/3
0.0584
TEa2/3
0.0543
ECT2/3
0.0531
PH
0.052
PMv
0.0516
PBG
0.0512
AUDv2/3
0.0505
AIv2/3
0.0488
LSc
0.0481
ORBm2/3
0.0474

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.328
Top-region fraction
0.094
Filter status
PASS

Interpretation limits