Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured astrocytes derived from neonatal rat brain exhibited high affinity, Na+-dependent, paroxetine and fluoxetine sensitive [3H]5-HT uptake. Reverse transcriptase-PCR demonstrated that astrocytes in culture expressed messenger RNA for the cloned serotonin transporter protein which has been characterised as the neuronal serotonin transporter. Although the serotonin transporter in cultured astrocytes displayed a Km value approximately 10 times greater than found in adult brain synaptosomes, these observations indicated that astrocytes in vitro may express the same serotonin transporter as neurons. Reverse transcriptase-PCR demonstrated the presence of serotonin transporter mRNA in the adult rat cerebral cortex, suggesting that astrocytes in vivo may express low levels of this mRNA. To investigate whether astrocytes in the adult CNS express functional serotonin transporters, glial plasmalemmal vesicles were prepared from cerebral cortex, representing a subcellular fraction composed primarily of vesicles derived from astrocytes. These vesicles were characterised by [3H]-glutamate and [3H]-dopamine uptake and by immunoblot analysis, using glial and synaptic markers: glutamate synthase, SNAP-25 and synaptobrevin. [3H]5-HT was taken up into glial plasmalemmal vesicles in a high affinity (Km approximately 40 nM), Na+ dependent, paroxetine-sensitive manner. The [3H]5-HT uptake capacity (Vmax) in these vesicles was approximately one quarter of that observed in synaptosomes. These data indicate that astrocytes in culture and in vivo are capable of 5-HT uptake via the previously characterised 'neuronal' serotonin transporter.
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PMID:Serotonin transporters in adult rat brain astrocytes revealed by [3H]5-HT uptake into glial plasmalemmal vesicles. 969 37

The function of soluble N-ethylmaleimide-sensitive attachment protein-alpha (alpha-SNAP) in exocytosis still remains obscure. This study was conducted to determine the physiological role of alpha-SNAP in the secretion of insulin and gamma-aminobutryric acid (GABA) from pancreatic beta cells. Reverse transcriptase-polymerase chain reaction analysis of total RNA isolated from rat islets disclosed alpha-SNAP, but not beta-SNAP, mRNA expression, and an immunofluorescence study of rat pancreas showed that alpha-SNAP was present predominantly in the cytoplasm of the islets of Langerhans. alpha-SNAP overexpression in rat islets enhanced insulin release relative to the control levels. An in vitro binding study showed that both wild-type alpha-SNAP and C-terminal-deleted alpha-SNAP mutant (1-285) can bind to syntaxin 1A. alpha-SNAP mutant (1-285) was overexpressed to evaluate its activity as dominant-negative effector on insulin release. Overexpression of alpha-SNAP mutant (1-285) in rat islets and MIN6 cells decreased glucose-stimulated insulin release to about 50% of the control levels. Suppression of endogeneous alpha-SNAP in MIN6 cells by treatment with an antisense phosphorothioate oligonucleotide resulted in inhibition of insulin release. In order to examine if alpha-SNAP functions in exocytosis from synaptic-like microvesicles in pancreatic beta cells, the functional role of alpha-SNAP in GABA release from MIN6 cells was studied. The data showed no effect of alpha-SNAP mutant (1-285) overexpression on GABA release. We conclude that 1) alpha-SNAP plays a crucial role in insulin exocytosis via large dense core vesicles, but not GABA released via synaptic-like microvesicles, in pancreatic beta cells; and 2) the interaction of alpha-SNAP and syntaxin 1A may play an important role in the insulin exocytotic process.
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PMID:alpha-soluble N-ethylmaleimide-sensitive factor attachment protein is expressed in pancreatic beta cells and functions in insulin but not gamma-aminobutyric acid secretion. 1007 5

The plant-specific Rop family GTPases are versatile molecular switches in many processes during plant growth, development, and responses to the environment. To understand how Rop achieves its functional versatility in signaling, we performed a genome-wide identification of putative Rop targets using a combination of the yeast two-hybrid method, bioinformatic tools, and a robust functional assay in pollen. In this study, we have identified 11 Arabidopsis genes encoding novel proteins, termed RICs (for Rop-interactive CRIB motif-containing proteins), that contain a CRIB (for Cdc42/Rac-interactive binding) motif required for their specific interaction with GTP-bound Rop1. RICs are divergent and classified into five groups that share little sequence homology outside of the conserved Rop-interactive domain. Overexpression in tobacco pollen tubes of the nine Ric genes that are expressed in Arabidopsis pollen causes distinct phenotypes, implying distinct functions for various RICs. RIC3 (group III) and RIC4 (group V) both cause depolarized growth like Rop1 and display Rop1-enhanced localization to the tip of pollen tubes, suggesting that these RICs may be two distinct targets of Rop1. In contrast, RIC10 (group I) promotes pollen tube elongation but does not affect pollen tube growth polarity and shows Rop1-independent localization to the cytoplasm, suggesting that RIC10 may participate in a Rop1-independent pathway probably controlled by a different Rop. Expression of all other RICs causes various degrees of growth inhibition in pollen tubes. Furthermore, these inhibitory RICs also exhibit distinct patterns of localization in pollen tubes. Our results suggest that various RICs have evolved to interact with Rops differentially and to perform distinct functions in pollen tubes. Reverse transcriptase-mediated polymerase chain reaction analysis showed that six of the nine RICs are expressed in various parts of Arabidopsis plants. On the basis of these observations, we propose that RICs function as Rop GTPase targets that control various Rop-dependent signaling pathways in plants.
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PMID:A genome-wide analysis of Arabidopsis Rop-interactive CRIB motif-containing proteins that act as Rop GTPase targets. 1175 91

Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC-IM) in the stomach and colon and ICC in the deep muscular plexus (ICC-DMP) of the small intestine. In the absence of ICC-IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC-IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse-associated proteins between nerve terminals and ICC-IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP-25 were detected. Synaptotagmin and SNAP-25-immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC-IM but not smooth muscle. W/W(V) mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC-IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP-25 were detected in W/W(V) tissues. In the absence of ICC-IM, synaptotagmin and SNAP-25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT-PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD-93 and PSD-95 in the stomach and expression levels of PSD-93 and PSD-95 were reduced in W/W(V) mutants. These data support the existence of synaptic specializations between enteric nerves and ICC-IM in gastric tissues. In the absence of ICC-IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals.
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PMID:Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach. 1625 30

We sequenced genes coding for components of the SNARE complex (STX1A, VAMP2, SNAP25) and their regulatory proteins (STXBP1/Munc18-1, SYT1), which are essential for neurotransmission, in 95 patients with idiopathic mental retardation. We identified de novo mutations in STXBP1 (nonsense, p.R388X; splicing, c.169+1G>A) in two patients with severe mental retardation and nonsyndromic epilepsy. Reverse transcriptase polymerase chain reaction and sequencing showed that the splicing mutation creates a stop codon downstream of exon-3. No de novo or deleterious mutations in STXBP1 were found in 190 control subjects, or in 142 autistic patients. These results suggest that STXBP1 disruption is associated with autosomal dominant mental retardation and nonsyndromic epilepsy.
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PMID:De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. 1955 57

Temporal lobe epilepsy is characterized by spontaneous recurrent seizures (SRS) and associated with behavioral problems. However, the molecular mechanisms underlying these problems are not yet clear. In this study, kainic acid (KA) was systemically administered to immature male Wistar rats to induce SRS. The behavior of the immature rats was evaluated with a water maze, elevated-plus mazes, and open field tests. The expression patterns of synaptophysin, SNAP-25, and synaptotagmin 1 (Syt 1) were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. KA-treated rats with SRS demonstrated learning and memory deficits, reduced anxiety, and increased locomotor activity, compared with placebo-treated rats and KA-treated rats without SRS. No neuronal cell loss was observed in the hippocampus 6 weeks after exposure to KA. However, RT-PCR and Western blot analyses revealed decreased synaptophysin, SNAP-25, and Syt 1 expression in KA-treated rats with SRS. Synaptophysin, SNAP-25, and Syt1 expression levels were found to be positively correlated with learning and memory but negatively correlated with anxiety and locomotor activity. These data suggested that SRS may induce changes in synaptophysin, SNAP-25, and Syt1 expression and may be functionally related to SRS-induced behavioral deficits.
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PMID:Abnormal expression of synaptophysin, SNAP-25, and synaptotagmin 1 in the hippocampus of kainic acid-exposed rats with behavioral deficits. 2483 94