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

Chem Biol Interact. 1999 May 14:119-120:29-42. doi: 10.1016/s0009-2797(99)00011-3.

Abstract

The molecular forms of acetylcholinesterase (AChE) correspond to various quaternary structures and modes of anchoring of the enzyme. In vertebrates, these molecules are generated from a single gene: the catalytic domain may be associated with several types of C-terminal peptides, that define distinct types of catalytic subunits (AChE(S), AChE(H), AChE(T)) and determine their post-translational maturation. AChE(S) generates soluble monomers, in the venom of Elapid snakes. AChE(H) generates GPI-anchored dimers, in Torpedo muscles and on mammalian blood cells. AChE(T) is the only type of catalytic subunit that exists in all vertebrate cholinesterases; it produces the major forms in adult brain and muscle. AChE(T) generates multiple structures, ranging from monomers and dimers to collagen-tailed and hydrophobic-tailed forms, in which catalytic tetramers are associated with anchoring proteins that attach them to the basal lamina or to cell membranes. In the collagen-tailed forms, AChE(T) subunits are associated with a specific collagen, ColQ, which is encoded by a single gene in mammals. ColQ contains a short peptidic motif, the proline-rich attachment domain (PRAD), that triggers the formation 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 synthetic polyproline shows a similar capacity to organize AChE(T) tetramers. Although the COLQ gene produces multiple transcripts, it does not generate the hydrophobic tail. P, which anchors AChE in mammalian brain membranes. The coordinated expression of AChE(T) subunits and anchoring proteins determines the pattern of molecular forms and therefore the localization and functionality of the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Acetylcholinesterase / genetics*
  • Acetylcholinesterase / metabolism
  • Acetylcholinesterase / physiology
  • Animals
  • Humans
  • Models, Molecular
  • Polymorphism, Genetic
  • Protein Conformation
  • Protein Processing, Post-Translational*

Substances

  • Acetylcholinesterase