Molecular Assembly and Biosynthesis of Acetylcholinesterase in Brain and Muscle: the Roles of t-peptide, FHB Domain, and N-linked Glycosylation

Vicky P Chen,Sherry L Xu,Ava J Y Guo,Roy C Y Choi,Karl W K Tsim,Wallace K B Chan,Wilson K W Luk,K Wing Leung,Gallant K L Chan

doi:10.3389/fnmol.2011.00036

Abstract

Acetylcholinesterase (AChE) is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ) or proline-rich membrane anchor (PRiMA). Complexes with ColQ represent the asymmetric forms (A12) in muscle, while complexes with PRiMA represent tetrameric globular forms (G4) mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs), having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins.

Highlights

Cholinesterases (ChEs) are serine hydrolases that preferentially act on choline esters
The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins
The physiological function of ChEs depends on the catalytic property of the enzymes and the restricted subcellular localization

Summary

MOLECULAR NEUROSCIENCE

Molecular assembly and biosynthesis of acetylcholinesterase in brain and muscle: the roles of t-peptide, FHB domain, and N-linked glycosylation. Complexes with ColQ represent the asymmetric forms (A12) in muscle, while complexes with PRiMA represent tetrameric globular forms (G4) mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs), having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization.

INTRODUCTION

MOLECULAR FORMS OF AChE AND BChE IN BRAIN AND MUSCLE