Termination and beyond: acetylcholinesterase as a modulator of synaptic transmission.
Termination of synaptic transmission by neurotransmitter hydrolysis is a substantial characteristic of cholinergic synapses. This unique termination mechanism makes acetylcholinesterase (AChE), the enzyme in charge of executing acetylcholine breakdown, a key component of cholinergic signaling. AChE is now known to exist not as a single entity, but rather as a combinatorial complex of protein products. The diverse AChE molecular forms are generated by a single gene that produces over ten different transcripts by alternative splicing and alternative promoter choices. These transcripts are translated into six different protein subunits. Mature AChE proteins are found as soluble monomers, amphipatic dimers, or tetramers of these subunits and become associated to the cellular membrane by specialized anchoring molecules or members of other heteromeric structural components. A substantial increasing body of research indicates that AChE functions in the central nervous system go far beyond the termination of synaptic transmission. The non-enzymatic neuromodulatory functions of AChE affect neurite outgrowth and synaptogenesis and play a major role in memory formation and stress responses. The structural homology between AChE and cell adhesion proteins, together with the recently discovered protein partners of AChE, predict the future unraveling of the molecular pathways underlying these multileveled functions.
Zimmerman
Gabriel
G
The Institute of Life Sciences and the Interdisciplinary Center for Neural Computation (ICNC), The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Soreq
Hermona
H
D000109:Acetylcholine / Q000235:genetics / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D006801:Humans; D008568:Memory / Q000502:physiology; D016501:Neurites / Q000201:enzymology*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary / Q000235:genetics; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D040681:Structural Homology, Protein; D013569:Synapses / Q000201:enzymology* / Q000235:genetics; D009435:Synaptic Transmission / Q000502:physiology*
D018377:Neurotransmitter Agents; D021122:Protein Subunits; D000110:Acetylcholinesterase; D000109:Acetylcholine