The Cholinergic Gene Locus

Abstract

Messenger RNAs and the cognate gene(s) entions require the protein machinery for ACh synthesis coding choline acetyltransferase (ChAT) and the vesicuand sequestration to be expressed in particular neurons lar acetyicholine transporter (VAChT) have been cloned at particular locations, including motor neurons, parafrom mammals and several other animal classes in the sympathetic autonomic neurons, brainstem reticular last decade. These have provided molecular tools for inactivating neurons, and basal forebrain projection nellvestigating acetylcholine synthesis and packaging into rons. synaptic vesicles, the genesis of cholinergic vesicles, andThe neurotransmitter properties of ACh were disthe development and senescence of the cholinergic nervous system. VAChT and ChAT have been found to share covered by Loewi (1921

The Vesicular Acetylcholine Transporter Interacts with Clathrin-associated Adaptor Complexes AP-1 and AP-2

“…It has been proposed, although not proven, that VAChT, along with synaptophysin (7), is trafficked from the trans-Golgi network (TGN) to the plasma membrane via the constitutive secretory pathway, then from the plasma membrane to an endosomal compartment, and finally from the endosomal compartment to SLMVs (6).…”

Neurochemical coding compared between varicose axons and cell bodies of myenteric neurons in the guinea-pig ileum

“…ChAT and VAChT are synthetic enzymes required for the synthesis and uptake of acetylcholine into synaptic vesicles, respectively [5]. The ChAT gene locus contains the entire sequence of VAChT cDNA, enabling transcription of VAChT and ChAT mRNA from the same or neighboring promoters [6].…”

“…The VAChT coding region is contained within the ChAT gene locus [6]. Transcription of both genes is controlled by the same or neighbouring promoters, which thereby coordinate expression of the two proteins, both of which are required to establish a cholinergic phenotype [5].…”

Beyond the usual suspects: a cholinergic route for panic attacks

“…The ChAT gene is part of a more complex genetic locus also coding for the vesicular acetylcholine transporter (VAChT) which packages transmitter into synaptic vesicles. 24 The genomic organization of these two distinct but related genetic functions is unique, and has been conserved from Drosophila to humans. 24 Recent animal studies clearly show that through a cascade of events stressful experiences can mediate neuronal plasticity by direct action upon the genetic expression of cholinergic muscarinic receptors in the relative long-term.…”

“…24 The genomic organization of these two distinct but related genetic functions is unique, and has been conserved from Drosophila to humans. 24 Recent animal studies clearly show that through a cascade of events stressful experiences can mediate neuronal plasticity by direct action upon the genetic expression of cholinergic muscarinic receptors in the relative long-term. Kaufer and colleagues 25 showed that acute stress of even moderate intensity (eg, a single session of 4 min forced swimming in mice)-as well as inhibitors of acetylcholinesterase (AChE)-produce a transient increase in the amount of released ACh in corticohippocampal areas, independent of the pituitary-adrenocortical axis.…”