Acetylcholinesterase (AChE) was the first identified synaptic component, characterized by its catalytic affinity for choline esters, and for a long time provided the conceptual scaffold for studies of the neuromuscular junction (NMJ). AChE was the first protein localized to the NMJ, in the 1930s, and its local expression shown to be regulated by the motoneuron in 1937. By the late 1940s a histochemical procedure was developed to visualize the enzyme at synapses, opening up a new era in the study of synaptic structure and function. This enzyme was also the first synaptic component to be purified, quantified, and later crystalized for structural and functional studies. Thus, historically, AChE has played a pivotal role in our understanding of NMJ development and function. AChE occurs in multiple oligomeric forms differing in their hydrophobic character and association with non-catalytic subunits that act as targeting sequences to insure correct localization at the cellular level. The predominant, if not unique, form of the enzyme responsible for terminating neuromuscular transmission is the collagen-tailed form of the enzyme attached to the synaptic basal lamina. This very large protein consists of three catalytic tetramers covalently linked to the three-stranded collagen-like tail (ColQ). The transcripts encoding AChE in muscle are preferentially expressed at sites of nerve-muscle contact and the AChE locally synthesized and assembled. Once externalized, the enzyme appears to be localized through interactions with the proteoglycan perlecan and subsequently covalently attached to the synaptic extracellular matrix. Thus a hierarchical series of events involving localized transcription and translation of the catalytic and non-catalytic subunits, localized assembly and secretion, and finally localized attachment to elements of the extracellular matrix insures that the enzyme is targeted to the correct location.
|Original language||English (US)|
|Number of pages||24|
|Journal||Journal of Neurocytology|
|State||Published - Jun 2003|
ASJC Scopus subject areas
- Cell Biology