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G(olf) in the basal ganglia.

S L Drinnan¹, B T Hope, T P Snutch

¹Kinsmen Laboratory of Neurological Sciences, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada, V6T 1 W5.

Molecular and Cellular Neurosciences

|November 17, 2009

Summary

The basal ganglia utilize a distinct G protein, G-alpha-olf (G(olf)), not previously known to be in this brain region, to stimulate adenylyl cyclase. This G(olf) protein is the primary stimulatory G protein in the basal ganglia, potentially mediating dopamine D1 receptor activity.

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Area of Science:

Neuroscience
Molecular Biology
Biochemistry

Background:

Guanine nucleotide-binding (G) proteins, specifically G(s), are crucial for mediating signals from neurotransmitter and hormone receptors to adenylyl cyclase.
Dopamine D1 receptors in the basal ganglia are known to stimulate adenylyl cyclase, traditionally attributed to G(s).

Purpose of the Study:

To investigate the specific G proteins involved in adenylyl cyclase stimulation in the rat basal ganglia.
To determine the identity and abundance of stimulatory G proteins in the striatum and related basal ganglia structures.

Main Methods:

Immunohistochemistry and immunoblotting to detect G protein levels.
Cholera toxin-dependent ADP ribosylation to assess G protein activity.
In situ hybridization and Northern blot analysis to quantify G protein mRNA expression.

Main Results:

Rat basal ganglia exhibit high levels of a G(salpha)-like protein distinct from G(s) found in other brain regions.
Striatum shows remarkably low messenger RNA (mRNA) levels for G(salpha).
High expression of G-alpha-olf (G(olf)) mRNA was discovered in the striatum, nucleus accumbens, and olfactory tubercle, with G(olf) transcripts being approximately 10-fold more abundant than G(salpha) transcripts in the striatum.

Conclusions:

G-alpha-olf (G(olf)) is not exclusive to olfactory neurons and is the predominant stimulatory G protein in the basal ganglia.
G(olf) likely plays a key role in coupling D1 dopamine receptors to adenylyl cyclase in the basal ganglia.