The polymorphism of acetylcholinesterase: post-translational processing, quaternary associations and localization

The molecular forms of acetylcholinesterase (AChE) correspond to various qu aternary structures and modes of anchoring of the enzyme. In vertebrates, t hese molecules are generated from a single gene: the catalytic domain may b e associated with several types of C-terminal peptides, that define distinc t types of catalytic subunits (AChE(S), AChE(H), AChE(T)) and determine the ir post-translational maturation. AChE, generates soluble monomers, in the venom of Elapid snakes. AChE(H) generates GPI-anchored dimers, in Torpedo m uscles and on mammalian blood cells. AChE(T) is the only type of catalytic subunit that exists in all vertebrate cholinesterases; it produces the majo r forms in adult brain and muscle. AChE(T) generates multiple structures, r anging from monomers and dimers to collagen-tailed and hydrophobic-tailed f orms, in which catalytic tetramers are associated with anchoring proteins t hat attach them to the basal lamina or to cell membranes. In the collagen-t ailed forms, AChE(T) subunits are associated with a specific collagen, ColQ , which is encoded by a single gene in mammals. ColQ contains a short pepti dic motif, the proline-rich attachment domain (PRAD), that triggers the for mation of AChE(T) tetramers, from monomers and dimers. The critical feature of this motif is the presence of a string of prolines, and in fact synthet ic polyproline shows a similar capacity to organize AChE(T) tetramers. Alth ough the COLQ gene produces multiple transcripts, it does not generate the hydrophobic tail, P, which anchors AChE in mammalian brain membranes. The c oordinated expression of AChE(T) subunits and anchoring proteins determines the pattern of molecular forms and therefore the localization and function ality of the enzyme. (C) 1999 Elsevier Science Ireland Ltd. All rights rese rved.