Heterotrimeric G proteins play central roles in signal transduction of neur
ons and other cells. The variety of their alpha-, beta-, and gamma-subunits
allows numerous combinations thereby confering specificity to receptor-G-p
rotein-effector interactions. Using antisera against individual G-protein b
eta-subunits we here present a regional and subcellular distribution of G b
eta(1), G beta(2), and G beta(5) in rat brain. Immunocytochemical specifici
ty of the subtype-specific antisera is revealed in Sf9 cells infected with
various G-protein beta-subunits. Since G beta-subunits together with a G-pr
otein gamma-subunit affect signal cascades we include a distribution of the
neuron-specific G gamma(2)- and G gamma(3)-subunits in selected brain area
s, G beta(1), G beta(2), and G beta(5) are preferentially distributed in th
e neuropil of hippocampus, cerebellum and spinal cord, G beta(2) is highly
concentrated in the messy fibres of dentate gyrus neurons ending in the str
atum lucidum of hippocampal CA3-area, High amounts of G beta(2) also occur
in interneurons innervating spinal cord alpha-motoneurons, G beta(5) is dif
ferentially distributed in all brain areas studied. It is found in the pyra
midal cells of hippocampal CA1-CA3 as well as in the granule cell layer of
dentate gyrus and in some interneurons. In the spinal cord G beta(5); in co
ntrast to G beta(2) concentrates around a-motoneurons, In cultivated mouse
hippocampal and hypothalamic neurons G beta(2) and G beta(5) are found in d
ifferent subcellular compartments. Whereas G beta(5) is restricted to the p
erikarya, G beta(2) is also found in processes and synaptic contacts where
it partially colocalizes with the synaptic vesicle protein sygnaptobrevin.
An antiserum recognizing G gamma(2) and G gamma(3) reveals that these subun
its are less expressed in hippocampus and cerebellum. Presumably this antis
erum specifically recognizes G gamma(2) and G gamma(3) in combinations with
certain G alpha s and/or G beta s.
The widespread but regionally and cellularly rather different distribution
of G beta- and G gamma(2/3)-subunits suggests that region-specific combinat
ions of G-protein subunits mediate signal transduction in the central nervo
us system. The different subcellular distribution of G beta-subunits in cul
tivated neurons reflects that observed in tissue where G beta(5) and G beta
(2) associate preferentially with the perikarya and the neuropil, respectiv
ely, and suggests an additional association of G beta(2) with secretory ves
icles.