G-proteins brain

As pointed out earlier in this article, T differs from other G proteins in that it is a peripheral membrane protein. After activation by Rho it seems to undergo subunit dissociation in which both its a subunit and its /3y complex dissociate from the Rho-containing membranes. Purification of brain G-proteins has shown that free a subunits of G0 and Gj are also water soluble, remaining in solution in the absence of detergents [74], The hydrophobicity of the whole ajSy G and Gj complexes was shown to be due to their j8y complexes 189]. Indeed, purified a subunits associate with phospholipid vesicles only if j8y complexes have been incorporated during vesicle formation [189]. Since the amino acid composition of T-/3 is equal to that of other G-j8s, but their ys differ, it follows that the principal role of y subunits should be to anchor non-T G proteins to the plasma membranes. This conclusion assumed, of course, that j8 subunits are not post-translationally modified in a tissue specific manner such that that they become water soluble in retinal photoreceptor cells and... 

Yamane, H. K., Farnsworth, C. C., Xie, H., Howald, W Fung, B. K.-K., Clarke, S Gelb, M. H Glomset, J. A. (1990). Brain G protein y subunits contain an all-manr-geranylgeranyl cysteine methyl ester at their carboxyl termini. Proc. Natl. Acad. Sci. USA 87,5868-5872. 

Kwon, G. Remmers, A. E. Datta, S. Neubig, R. R. Synthesis and characterization of fluorescently labeled hovine brain G protein subunits. Biochemistry 1993, 32, 2401-2408. 

Glutamate is a small amino acid which constitutes the most important neurotransmitter at excitatory synapses in the mammalian brain. Glutamate can act on several different types of receptors including cation channels and G-protein-coupled receptors. 

Neurotrophins (NGF brain-derived neurotrophic factor, BDNF neurotrophin-3, NT-3 NT-4 NT-6) are important regulators of neural survival, development, function, and plasticity of the vertebrate nervous system [1]. Neurotrophins generally function as noncovalently associated homodimers. They activate two different classes of receptors, through which signaling pathways can be activated, including those mediated by Ras and members of the cdc42/rac/rho G protein families, MAP kinase, PI-3 kinase, and Jun kinase cascades. 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

Harrison JK, Barber CM, Lynch KR (1994) cDNA cloning of a G-protein-coupled receptor expressed in rat spinal cord and brain related to chemokine receptors. Neurosci Lett 169 85-89 Harrison JK, Jiang Y, Chen S et al (1998) Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia. Proc Natl Acad Sci USA 95 10896-10901... 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

Halpem M., Shapiro L.S. and Jia C.P. (1995). Differential localisation of G-proteins in opossum vomeronasal system. Brain Res 677, 157-161. 

Jia C. and Halpem M. (1996). Subclasses of vomeronasal receptor neurons differential expression of G-proteins (Gi-alpha2 Go-alpha) and segregated projections to the accessory olfactory-bulb. Brain Res 719, 117-128. 

Saito H., Mimmack M., Keveme E.B., Kishimoto J. and Emson P. (1998). Isolation of mouse vomeronasal receptor genes and their co-localization with specific G-protein messenger RNAs. Molec Brain Res 60, 215-227. 

Wekesa K. and Anholt R. (1999). Differential expression of G-proteins in the mouse olfactory system. Brain Res 837, 117-126. 

---