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

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.

Radiometric assay of ghrelin hydrolase activity and 3H-ghrelin distribution into mouse tissues

“…Because mouse BChE exhibits a 10-fold lower K m and 3-fold higher k cat than human BChE we conclude that ghrelin docking in the active site must differ widely across species. In human BChE, oddly, ghrelin hydrolysis is affected by the C-terminus, which promotes BChE oligomerization [34, 35] but hasn't been thought to participate in catalysis. Deleting the C-terminus does not affect enzymatic activity with butyrylthiocholine, benzoylcholine, or nitrophenylbutyrate [34], although it enhances protein expression and protects nascent BChE from degradation in the endoplasmic reticulum [36].…”

Rescue and Stabilization of Acetylcholinesterase in Skeletal Muscle by N-terminal Peptides Derived from the Noncatalytic Subunits

“…The mechanisms responsible for the activation and stabilization of AChE subunits into catalytically active oligomers are being elucidated. For example, co-assembly of the noncatalytic ColQ and PRiMA subunits are essential for the assembly of higher order oligomeric forms such as the tetramers and the asymmetric collagen-tailed forms (14,28,29), and this occurs through the PRAD-containing N-terminal domain (7)(8)(9).…”

Mouse Acetylcholinesterase Enhances Neurite Outgrowth of Rat R28 Cells Through Interaction With Laminin-1

“…The PAS lies at the entrance of the active site gorge of AChE, and it is probably involved in protein-protein interactions [4], [23], [30]–[34], as well as in cell-substrate adhesion [32], [35], including deposition of beta-amyloid in Alzheimer's disease [36], [37]. The C-terminal t-peptide appears to increase apoptosis [38] and is interacting with ColQ and PRiMA [39]. The ARP peptide promotes neuronal development and plasticity [40].…”