Choline acetyltransferase (ChAT) catalyzes the synthesis of the neurotransmitter acetylcholine (ACh) from choline and acetyl-CoA in cholinergic neurons. ChAT serves as a specific marker for cholinergic neurons in both peripheral and central nervous systems. Dysfuntion of cholinergic neurons underlies aspects of clinical symptoms found in neurological and psychiatric disorders such as Alzheimer’s disease, Down and Rett syndromes.
Evidence shows that the enzyme choline-O-acetyltransferase (ChAT) exists in two forms inside cholinergic nerve terminals, a soluble hydrophilic form and the membrane-associated amphiphilic form. As an example, membrane-bound ChAT was shown to be localized as a peripheral protein that is attached to synaptosomal plasma membrane (Gabrielle et al. 2003). Membrane-bound ChAT has served as the feature condition that allows Advanced Targeting Systems to apply their technology through an affinity-purified antibody to ChAT conjugated to saporin, the ribosome-inactivating protein, to specifically target and eliminate those specific cells.
Anti-ChAT-SAP is made with an antibody using a 22-amino acid peptide from porcine ChAT (GLF SSY RLP GHT QDT LVA QKSS). The targeted toxin recognizes porcine ChAT and is expected to cross-react with rat, mouse, and human.
Gabrielle P, Jeana M, Lorenza EC (2003) Cytosolic choline acetyltransferase binds specifically to cholinergic plasma membrane of rat brain synaptosomes to generate membrane-bound enzyme. Neurochem Res 28(3-4):543-549.