Neural expression of a novel alternatively spliced and polyadenylated Gs alpha transcript

Crawford, Jacqueline; Mutchler, K J; Sullivan, Brian E.; Lanigan, Thomas M.; Clark, Michael; Russo, Andrew F.

doi:10.1016/s0021-9258(18)98427-9

Cited by 47 publications

(1 citation statement)

References 52 publications

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“…These four alternative transcripts show tissue-dependent alternative splicing and may provide different regulatory properties (Kozasa et al 1988;Novotny and Svoboda 1998). In addition, an alternative splicing of exon 3 occurs onto exon N1, which is located in intron 3, leading to the formation of a C-terminally truncated Gsa protein that is expressed in neural tissues (Crawford et al 1993).…”

Section: Gsa Transcriptmentioning

confidence: 99%

Guanine Nucleotide Binding Protein (G Protein), Gamma

2018

Encyclopedia of Signaling Molecules

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G alpha o 1893G regulators of the Gao protein may provide a cellspecific mechanism for Gao-regulated signaling pathways. PTX catalyzes the ADP-ribosylation of the a subunits of the Go, Gi, and Gt proteins at the C-terminal cysteine residue (À4 position). This prevents the G protein from interacting with GPCRs on the cell membrane, thus interfering with intracellular signaling. 1896 G alpha o G alpha o 1897 G cyclase, guanylate cyclase, Rap1 GTPaseactivating protein (Rap1GAP), axin, and pins. Compartmentalization of these signaling molecules in membrane rafts may ensure specificity and fidelity in Gao signaling. Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane proteins in the mammalian brain. Go regulates neuronal development, memory, visual reception, olfactory reception, and taste reception. It is also localized in heart tissue and implicated in heart contractility. Its expression is regulated during the development of the brain and heart. Somatic mutations in the GNAO1 gene induce human cancers by rendering Gao constitutively activated. Heterozygous mutations in the GNAO1 gene cause epileptic encephalopathy by destabilizing Gao. Gao-deficient mice have several neurological deficits, including tremors, seizures, hyperalgesia, motor control impairment, and olfactory impairment. Muscarinic regulation of heart rate and heart rate variability is also impaired in Gao-deficient mice. Drosophila melanogaster mutants with loss of function of Gao show impaired morphogenesis of the heart and epithelial polarity of cardiac cells and abnormal sleep. Gao-deficient C. elegans has phenotypes including neuronal migration defects, hyperactive locomotion, and egg laying.

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Section: Gsa Transcriptmentioning

confidence: 99%

Guanine Nucleotide Binding Protein (G Protein), Gamma

2018

Encyclopedia of Signaling Molecules

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BDNF induction of tryptophan hydroxylase mRNA levels in the rat brain

et al. 1998

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We have previously demonstrated an augmentation of serotonergic activity within various brain areas following infusion of brain-derived neurotrophic factor (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe nuclei (PAG/DR). However, the mechanism of this BDNF-induced modulatory effect on serotonergic systems was unclear. The aim of the present work was to study the regulation of tryptophan hydroxylase (TPH) mRNA levels after chronic BDNF administration in vivo. TPH mRNA levels were measured using a quantitative competitive reverse transcription polymerase chain reaction (RT-PCR) assay. A significant increase in the expression of TPH mRNA (13-fold) was found within the PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained throughout the duration of infusion (11 days). This was accompanied by increased serotonin (5-hydroxytryptamine, 5-HT) levels and decreased nociceptive responsiveness assessed by tail-flick latency. BDNF induction of TPH mRNA levels was also observed in a serotonergic cell line derived from raphe neurons, indicating that BDNF can directly regulate TPH mRNA levels. These results suggest that BDNF augments 5-HT synthesis in vivo by directly enhancing steady-state TPH mRNA levels, and subsequently leading to marked behavioral alterations.

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