Cacng1

Voltage-dependent calcium channel gamma-1 subunit (Dihydropyridine-sensitive L-type, skeletal muscle calcium channel subunit gamma)

Spatial tier: RESTRICTED · Class: ION_CHANNEL · Top region: CP (Caudoputamen) · Positive regions: 24/554

43.7Discovery Score
35.8Targetability Score
CEvidence grade C
What this means: Cacng1: fine CCF profile is restricted toward CP (top regions: CP, RH, AMd, Eth, IMD; 24 positive regions); direct spatial validation is still required.

Function in CP: evidence, prediction, innovation

Gene function
CACNG1 encodes the gamma-1 subunit of the skeletal-muscle L-type (dihydropyridine-receptor) calcium channel. It is a four-transmembrane auxiliary subunit that acts as an endogenous calcium antagonist, accelerating inactivation and shifting the steady-state inactivation of CaV1.1 to more negative potentials. It is the founding member of the gamma-subunit family from which the brain TARPs (CACNG2-8, stargazin and relatives) that traffic AMPA receptors were named, but gamma-1 itself has no established TARP activity.
Region function
The caudoputamen is the dorsal striatum: GABAergic D1 direct-pathway and D2 indirect-pathway spiny projection neurons receive massive cortical glutamate and nigral dopamine and control action selection, habit formation and motor vigour.
Published in this region
inferred No region-specific literature found. Gamma-1 is characterised only in skeletal muscle (Arikkath et al. 2003; Andronache et al. 2007), and the gamma-subunit gene-family surveys that established brain expression patterns (Burgess et al. 1999, 2001) assign striatal and forebrain expression to the TARP members gamma-2, gamma-3, gamma-4, gamma-7 and gamma-8 rather than to gamma-1.
Predicted function
Prediction: if gamma-1 protein really is present in caudoputamen it would most plausibly act, as it does in muscle, as a brake on L-type calcium channels - here CaV1.2/CaV1.3 in spiny projection neurons - damping dendritic calcium entry and the L-type-dependent component of dopamine-driven plasticity. Striatal Cacng1 deletion is predicted to increase L-type calcium current and enhance LTP at corticostriatal synapses, producing exaggerated psychostimulant-induced locomotor sensitisation; the phenotype should be occluded by the L-type blocker isradipine. This prediction carries a strong caveat that the mapped signal may be a cross-hybridisation or low-level artefact.
Innovation
★★★☆☆ 3/5 Nothing is published on gamma-1 in striatum and tools exist, but the low biological plausibility of a skeletal-muscle-restricted subunit in spiny neurons limits the expected payoff.
Tools
Cacng1 knockout mice (viable, characterised in muscle physiology); IMPC Cacng1 alleles; dihydropyridines nifedipine, isradipine and Bay K 8644 to manipulate the partner channel; anti-CACNG1 antibodies; Drd1-Cre and Adora2a-Cre for pathway-specific striatal deletion.
References

Direct evidence located at the region

Cacng1 Allen ISH at the CCF centroid of CP

Allen ISH experiment 69236945, section image 69225935 (section 142): the section that contains the CCF centroid of Caudoputamen 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

Cacng1 Allen ISH at the CCF centroid of CP

Allen ISH experiment 77793163, section image 77787110 (section 154): the section that contains the CCF centroid of Caudoputamen 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 Cacng1Allen reference atlas: CP (structure 672)ABC Atlas MERFISH viewer(in the ABC Atlas choose dataset MERFISH-C57BL6J-638850-CCF, colour cells by gene "Cacng1" or by parcellation_substructure "CP")All genes confined to CP + 3-D brain

Direct spatial evidence

MERFISH REGION LOCATOR
CP MERFISH region locator
Real single-cell MERFISH coordinates for the CP (Caudoputamen) 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

Cacng1 regional expression profile

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

Spatial profile

CP
0.372
RH
0.23
AMd
0.215
Eth
0.209
IMD
0.209
PR
0.206
CL
0.201
IAM
0.191
LP
0.191
AMv
0.183
RE
0.182
MD
0.182
BLAp
0.173
IAD
0.173
SMT
0.167
SGN
0.157
DR
0.153
MEPO
0.153
PN
0.147
CM
0.146

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.313
Top-region fraction
0.064
Filter status
PASS

Interpretation limits