Specific Vesicular Acetylcholine Transporter Promoters Lie within the First Intron of the Rat Choline Acetyltransferase Gene

Cervini, Riccardo; Houhou, Leila; Pradat, Pierre-Fran ̧ois; Bejanin, Stéphane; Mallet, Jacques; Berrard, Sylvie

doi:10.1074/jbc.270.42.24654

Cited by 77 publications

(46 citation statements)

References 17 publications

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“…In addition, distribution of ChAT and VAChT mRNAs in the adult rat brain is virtually identical (3), suggesting coordinate regulation of these two genes even though specific promoters for ChAT and VAChT may exist (18). ChAT and FIG.…”

Section: Discussionmentioning

confidence: 99%

“…The regulatory strategies and mechanisms identified for Drosophila ChAT expression should be also applicable to expression of another cholinergic marker, VAChT. In contrast to this simple situation in Drosophila, some mammalian VAChT transcripts have been reported to share sequence with ChAT while others do not (18). These latter VAChT transcripts apparently use alternative promoters.…”

Section: Discussionmentioning

confidence: 99%

“…ChAT mRNA (18). To examine the possibility that such mRNAs may also be present in Drosophila an RNase protection assay was carried out with a probe that included the boundary sequence of the shared first exon and the unique VAChT second exon (Fig.…”

Section: Vacht Mrna Is Present Only In a Form Which Includes The Sharmentioning

confidence: 99%

“…In C. elegans, alternative splicing of a common precursor RNA is proposed to be responsible for producing two distinct mRNAs from the cholinergic locus (16). In vertebrates, however, it is likely that ChAT and VAChT specific mRNAs result from a combination of differential promoter usage and/or alternative RNA processing (3,5,17,18).…”

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confidence: 99%

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Structure and Organization of the DrosophilaCholinergic Locus

Kitamoto

Wang

Salvaterra

1998

Journal of Biological Chemistry

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The Drosophila cholinergic locus is composed of two distinct genetic functions: choline acetyltransferase (ChAT; EC 2.3.1.6), the enzyme catalyzing biosynthesis of neurotransmitter acetylcholine (ACh), and the vesicular ACh transporter (VAChT), the synaptic vesicle membrane protein which pumps transmitter into vesicles. Both genes share a common first exon and the remainder of the VAChT gene contains a single coding exon residing entirely within the first intron of ChAT. RNase protection analysis indicates that all Drosophila VAChT specific transcripts contain the shared first exon and suggests common transcriptional control for ChAT and VAChT. Similar types of genomic organization have been evolutionarily conserved for cholinergic loci in nematodes and vertebrates, and may operate to ensure coordinate expression of these functionally related genes in the same cells. The relative levels of Drosophila ChAT and VAChT mRNA differ, however, in different tissues or in Cha mutants, indicating that independent regulation of ChAT and VAChT transcripts may occur post-transcriptionally. The predicted Drosophila VAChT protein is composed of 578 amino acids and contains 12 conserved putative transmembrane domains. Full-length VAChT cDNA is 7.2 kilobase long and has unusually long 5-and 3-untranslated regions (UTR). The 5-UTR contains a GTG ChAT translational initiation codon along with three other potential ATG initiation codons. These features of the VAChT 5-UTR region suggest that a ribosome scanning model may not be used for VAChT translation initiation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Vacht Mrna Is Present Only In a Form Which Includes The Sharmentioning

confidence: 99%

mentioning

confidence: 99%

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Structure and Organization of the DrosophilaCholinergic Locus

Kitamoto

Wang

Salvaterra

1998

Journal of Biological Chemistry

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“…The cholinergic gene locus contains the genes for both the enzyme choline acetyltransferase (ChAT; EC 2.3.1.6) and the vesicular acetylcholine transporter (VAChT) (1,2,5). ChAT is the enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine, while VAChT is the vesicle membrane transporter that translocates cytoplasmic acetylcholine to the interior of synaptic vesicles.…”

mentioning

confidence: 99%

Protein Kinase A Regulates Cholinergic Gene Expression in PC12 Cells: REST4 Silences the Silencing Activity of Neuron-Restrictive Silencer Factor/REST

Shimojo

Paquette²,

Anderson

et al. 1999

Molecular and Cellular Biology

113

112

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Vesicular acetylcholine transporter (VAChT) protein: A novel and unique marker for cholinergic neurons in the central and peripheral nervous systems

et al. 1997

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Acetylcholine (ACh) is synthesized in nerve terminals from choline and acetyl coenzyme A by the cytoplasmic enzyme choline acetyltransferase (ChAT). The neurotransmitter is thereafter transported into synaptic vesicles, where it is stored until release. cDNA clones encoding a vesicular ACh transporter (VAChT) were recently isolated. In this paper, we report on the generation of highly specific goat polyclonal antisera to the rat VAChT protein by using a synthetic carboxy-terminal 20-amino-acid peptide sequence as an immunogen. Characterization of the antisera revealed recognition of VAChT, but not vesicular monoamine transporter (VMAT) protein, in transfected CV-1 cells. VAChT immunoreactivity was also detected in cells that endogenously express the protein, such as in PC12 cells and in primary cultures of spinal motoneurons. Absorption controls showed that the VAChT antisera could be completely blocked at the 10(-5) M concentration by cognate peptide used for immunization. The antisera cross-reacted with the VAChT protein in rat and mouse but not in guinea pig, rabbit, or cat. Immunohistochemistry and confocal laser microscopy, using the goat VAChT antisera, showed strong immunoreactivity in discrete fibers and neuronal cell bodies of the central and peripheral nervous systems. Within cell bodies and axonal nerve terminals, as well as in dendrites, the staining appeared granular, presumably representing labeling of synaptic vesicles containing ACh. In the rat central nervous system, VAChT-positive cell bodies were demonstrated in the cerebral cortex, striatum, septum, nucleus basalis, medial habenula, mesopontine complex, cranial, and autonomic and spinal motor nuclei and in the intermediomedial region near the central canal. High densities of VAChT-immunoreactive axonal fibers were encountered in areas such as the olfactory bulb, cerebral cortex, striatum, basal forebrain, amygdala, thalamus, hypothalamus including median eminence, hippocampal formation, superior colliculus, interpeduncular nucleus, and pedunculopontine and laterodorsal tegmental nuclei. In cranial and spinal motor nuclei, particularly large varicosities were seen in close proximity to the motoneuron cell somata and their proximal dendrites. In the peripheral nervous system, VAChT immunoreactivity was also detected in motor endplates of skeletal muscle as well as in fibers of sympathetic and parasympathetic abdominal ganglia, heart atrium, respiratory tract, gastrointestinal tract, pancreas, adrenal medulla, male genitourinary tract, and salivary and lacrimal glands. Direct double labeling revealed colocalization of VAChT and ChAT immunoreactivity in neurons. The results show that VAChT antisera represent novel and unique tools for the study of cholinergic neurons in the central and peripheral nervous systems.

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Specific Vesicular Acetylcholine Transporter Promoters Lie within the First Intron of the Rat Choline Acetyltransferase Gene

Cited by 77 publications

References 17 publications

Structure and Organization of the DrosophilaCholinergic Locus

Structure and Organization of the DrosophilaCholinergic Locus

Protein Kinase A Regulates Cholinergic Gene Expression in PC12 Cells: REST4 Silences the Silencing Activity of Neuron-Restrictive Silencer Factor/REST

Vesicular acetylcholine transporter (VAChT) protein: A novel and unique marker for cholinergic neurons in the central and peripheral nervous systems

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