Cholinergic neurons are best characterized by the enzyme choline
acetyltransferase (CHAT; EC 2.3.1.6 ), which catalyzes the biosynthesis of acetylcholine.Cholinergic neurotransmission requires uptake of extracellular choline, biosynthesis of acetylcholine from choline and
acetyl-coenzyme A, accumulation of acetylcholine into synaptic vesicles driven by proton antiport, and quantal release
of acetylcholine from synaptic vesicles triggered by electrical depolarization of the cholinergic neuron. Erickson et al. (1994) found that the VACHT gene mapped to the same
chromosomal location, 10q11.2. The entire sequence of the human VACHT cDNA was contained uninterrupted within
the first intron of the CHAT gene locus. Transcription of VACHT and CHAT mRNA from the same or contiguous
promoters within the single regulatory locus provided a previously undescribed genetic mechanism for coordinate
regulation of 2 proteins whose expression is required to establish a mammalian neuronal phenotype.
Gene whose expression is detected by cDNA array hybridization: transcription factors, cell signaling and extracellular communication Rozenn Dalbi?Tran and Pascal Mermilloda
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa, Luteal cells
Comment
Fritz S, et al reported the evidence for expression of
choline-acetyltransferase and vesicular acetylcholine transporter
in human granulosa-luteal cells.
The authors demonstrated the ability of muscarinic agonists to stimulate the proliferation of
human GC within 24 h. In vivo, ACh, the natural ligand of these receptors is
thought to be contained in cholinergic nerve fibers innervating the ovary.
Surprisingly, the prerequisite for the synthesis of ACh, the enzyme
choline-acetyltransferase (ChAT), is also expressed by human GC, as shown by Western blotting and immunocytochemistry. In addition, these cells express
another marker for ACh synthesis, namely the gene for the vesicular acetylcholine
transporter, as evidenced by RT-PCR cloning, Western blotting, and
immunocytochemistry. The data identify the M1 receptor in human
GC and point to a novel, trophic role of the neurotransmitter ACh. Furthermore,
the presence of the prerequisites of ACh synthesis in human GC indicate that an
autocrine/paracrine regulatory loop also exists in the in vivo counterparts of these
cells in the ovary, i.e. in the cells of the preovulatory follicle and/or of the young
corpus luteum.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Survival Role of Locally Produced Acetylcholine in the Bovine Corpus Luteum. Al-Zi'abi MO et al. The present study was conducted to explore the source of acetylcholine (ACH) in the corpus luteum (CL) and to test our hypothesis of anti-apoptotic role of ACH in the bovine CL, and further to investigate whether nerve growth factor (NGF), insulin like growth factor 1 (IGF1) and transforming growth factor beta 1 (TGFB1) influence the expression of choline acetyltransferase (CHAT), the biosynthetic enzyme of ACH, in cultured bovine luteal cells. Protein expression and immunolocalization of CHAT were carried out at different stages throughout the luteal phase and in cultured luteal and endothelial cells. ACH was measured in luteal tissue at the different luteal stages and in luteal cells cultured for 8 h and 24 h. Cell viability and TUNEL assays were performed on cultured mid luteal cells treated with or without tumor necrosis factor alpha (TNF)/interferon gamma (IFNG) in the presence of ACH and its muscarinic (atropine) and nicotinic (mecamylamine) receptor antagonists. The CL was devoid of cholinergic nerve fibers. CHAT immunostaining was evident in luteal, endothelial and stromal cells in luteal tissue sections and in cultured luteal and endothelial cells. CHAT protein was expressed throughout the cycle without any significant changes. ACH concentration in luteal tissue was not changed during the luteal stages, but increased over time and with increased cell numbers in luteal cell cultures. ACH increased cell viability and prevented cell death induced by TNF/IFNG. Atropine significantly attenuated ACH action whereas mecamylamine had no effect. TNF/IFNG treatment downregulated CHAT expression while NGF, IGF1 and TGFB1 upregulated CHAT expression in cultured luteal cells. The overall findings strongly suggest a non-neural source and anti-apoptotic role of ACH in the bovine CL. Locally produced ACH appears to be regulated by NGF, IGF1 and TGFB1.