Cloning of the Rat Gene Encoding Choline Acetyltransferase, a Cholinergic Neuron-specific Marker

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 May 15

PMID 1584771

Citations 10

Authors

M Hahn

S L Hahn

D M Stone

T H Joh

Affiliations

Soon will be listed here.

Abstract

The neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT; EC 2.3.1.6). Since the expression of ChAT in the nervous system is restricted to cholinergic neurons, it serves as a specific marker for these neurons. In Alzheimer disease, ChAT activity is markedly reduced in the affected brain areas. Nerve growth factor can increase the ChAT activity of brain cholinergic neurons in vitro and in vivo. We have cloned the rat ChAT gene and identified one 5' noncoding exon and 14 exons that account for the entire coding sequence. The exon organization is compared with the protein domains conserved during evolution. These exons are distributed over at least 64 kilobases in the rat genome; the largest intron is at least 14 kilobases long. Within a 0.7-kilobase region immediately upstream of the confirmed sequence of the noncoding exon, TATA-like elements and numerous potential binding sites for transcription factors are found, including AP-1, Sp1, octamer-binding factor(s), CTF/NF-1, and the nuclear oncoprotein Myb.

Citing Articles

Acute myocardial infarction induces remodeling of the murine superior cervical ganglia and the carotid body.

Ge Y, van Roon L, van Gils J, Geestman T, van Munsteren C, Smits A Front Cardiovasc Med. 2022; 9:758265.

PMID: 36277772 PMC: 9582601. DOI: 10.3389/fcvm.2022.758265.

Functional characterization of intrinsic cholinergic interneurons in the cortex.

von Engelhardt J, Eliava M, Meyer A, Rozov A, Monyer H J Neurosci. 2007; 27(21):5633-42.

PMID: 17522308 PMC: 6672773. DOI: 10.1523/JNEUROSCI.4647-06.2007.

Choline acetyltransferase: regulation and coupling with protein kinase and vesicular acetylcholine transporter on synaptic vesicles.

Sha D, Jin H, Kopke R, Wu J Neurochem Res. 2004; 29(1):199-207.

PMID: 14992279 DOI: 10.1023/b:nere.0000010449.05927.f9.

Demonstration of cholinergic ganglion cells in rat retina: expression of an alternative splice variant of choline acetyltransferase.

Yasuhara O, Tooyama I, Aimi Y, Bellier J, Hisano T, Matsuo A J Neurosci. 2003; 23(7):2872-81.

PMID: 12684474 PMC: 6742087.

Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice.

Brandon E, Lin W, DAmour K, Pizzo D, Dominguez B, Sugiura Y J Neurosci. 2003; 23(2):539-49.

PMID: 12533614 PMC: 6741871.

References

Hahn S, Hahn M, Joh T . Genomic organization of the rat aromatic L-amino acid decarboxylase (AADC) locus: partial analysis reveals divergence from the Drosophila dopa decarboxylase (DDC) gene structure. Mamm Genome. 1991; 1(3):145-51. DOI: 10.1007/BF00351060. View

MOSCOVICI C . Leukemic transformation with avian myeloblastosis virus: present status. Curr Top Microbiol Immunol. 1975; 71:79-101. DOI: 10.1007/978-3-642-66193-8_2. View

Finocchiaro G, Taroni F, Rocchi M, Martin A, Colombo I, Tarelli G . cDNA cloning, sequence analysis, and chromosomal localization of the gene for human carnitine palmitoyltransferase. Proc Natl Acad Sci U S A. 1991; 88(2):661-5. PMC: 50872. DOI: 10.1073/pnas.88.2.661. View

Sugihara H, Andrisani V, Salvaterra P . Drosophila choline acetyltransferase uses a non-AUG initiation codon and full length RNA is inefficiently translated. J Biol Chem. 1990; 265(35):21714-9. View

Rosenfeld M . POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991; 5(6):897-907. DOI: 10.1101/gad.5.6.897. View

Bartel D, Sheng M, Lau L, Greenberg M . Growth factors and membrane depolarization activate distinct programs of early response gene expression: dissociation of fos and jun induction. Genes Dev. 1989; 3(3):304-13. DOI: 10.1101/gad.3.3.304. View

Ness S, Marknell A, Graf T . The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell. 1989; 59(6):1115-25. DOI: 10.1016/0092-8674(89)90767-8. View

Biedenkapp H, Borgmeyer U, Sippel A, Klempnauer K . Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988; 335(6193):835-7. DOI: 10.1038/335835a0. View

Kyriakis J, Hausman R, Peterson S . Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc Natl Acad Sci U S A. 1987; 84(21):7463-7. PMC: 299316. DOI: 10.1073/pnas.84.21.7463. View

10.

Fukada K . Purification and partial characterization of a cholinergic neuronal differentiation factor. Proc Natl Acad Sci U S A. 1985; 82(24):8795-9. PMC: 391524. DOI: 10.1073/pnas.82.24.8795. View

11.

Brice A, Berrard S, Raynaud B, Ansieau S, Coppola T, Weber M . Complete sequence of a cDNA encoding an active rat choline acetyltransferase: a tool to investigate the plasticity of cholinergic phenotype expression. J Neurosci Res. 1989; 23(3):266-73. DOI: 10.1002/jnr.490230304. View

12.

McManaman J, Crawford F, STEWART S, Appel S . Purification of a skeletal muscle polypeptide which stimulates choline acetyltransferase activity in cultured spinal cord neurons. J Biol Chem. 1988; 263(12):5890-7. View

13.

Berrard S, Brice A, Lottspeich F, Braun A, Barde Y, Mallet J . cDNA cloning and complete sequence of porcine choline acetyltransferase: in vitro translation of the corresponding RNA yields an active protein. Proc Natl Acad Sci U S A. 1987; 84(24):9280-4. PMC: 373252. DOI: 10.1073/pnas.84.24.9280. View

14.

Gearing D, Gough N, King J, Hilton D, Nicola N, Simpson R . Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 1987; 6(13):3995-4002. PMC: 553879. DOI: 10.1002/j.1460-2075.1987.tb02742.x. View

15.

Yamamori T, Fukada K, Aebersold R, Korsching S, Fann M, Patterson P . The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989; 246(4936):1412-6. DOI: 10.1126/science.2512641. View

16.

Mitchell P, Tjian R . Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989; 245(4916):371-8. DOI: 10.1126/science.2667136. View

17.

Ishii K, Oda Y, Ichikawa T, Deguchi T . Complementary DNAs for choline acetyltransferase from spinal cords of rat and mouse: nucleotide sequences, expression in mammalian cells, and in situ hybridization. Brain Res Mol Brain Res. 1990; 7(2):151-9. DOI: 10.1016/0169-328x(90)90092-r. View

18.

Alderson R, Alterman A, Barde Y, Lindsay R . Brain-derived neurotrophic factor increases survival and differentiated functions of rat septal cholinergic neurons in culture. Neuron. 1990; 5(3):297-306. DOI: 10.1016/0896-6273(90)90166-d. View

19.

Ziff E . Nerve growth factor regulates tyrosine hydroxylase gene transcription through a nucleoprotein complex that contains c-Fos. Genes Dev. 1990; 4(4):477-91. DOI: 10.1101/gad.4.4.477. View

20.

Askanas V, Engel W . Thyrotropin-releasing hormone enhances choline acetyltransferase and creatine kinase in cultured spinal ventral horn neurons. J Neurochem. 1984; 43(2):586-9. DOI: 10.1111/j.1471-4159.1984.tb00939.x. View