Transcriptional control of different subunits of AChE in muscles: signals triggered by the motor nerve-derived factors.
Acetylcholinesterase (AChE) is a highly polymorphic enzyme. Alternative splicing in the 3' region of the primary transcript generates different subunits that contain the same catalytic domain but with distinct carboxyl termini. In mammals, the AChE(R) variant produces a soluble monomer that is up-regulated in the brain during stress. The AChE(H) variant produces a GPI-anchored dimer that is mainly expressed in blood cells, while AChE(T) variant is largely predominant in the brain and muscle. AChE(T) subunits associate with a collagen tail subunit (ColQ) forming asymmetric AChE species (A(4), A(8), and A(12) AChE) in muscle, and also form amphiphilic tetramers associated with a proline-rich membrane anchor (PRiMA) as globular AChE (G(4) AChE) in brain and muscle. The formation of these AChE forms depends on the physiological status of the muscles, and on the innervating nerves. The motor nerves achieve this regulation by two distinct mechanisms: release of the trophic factor calcitonin gene-related peptide (CGRP) and nerve-evoked electrical activity, which differentially regulate the expression levels of AChE(T), PRiMA and ColQ via different downstream signaling cascades. The regulatory mechanisms provided by the nerve are important to account for the different expression patterns of AChE and associated proteins in fast- and slow-twitch muscles.
Tsim
Karl W K
KW
Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Kowloon, Hong Kong SAR, China. BOTSIM@UST.HK
Choi
Roy C Y
RC
Xie
Heidi Q
HQ
Zhu
Judy T T
JT
Leung
K Wing
KW
Lau
Faye T C
FT
Chu
Glanice K Y
GK
Chen
Vicky P
VP
Mok
Mokka K W
MK
Cheung
Anna W H
AW
Bi
Cathy W C
CW
D000110:Acetylcholinesterase / Q000235:genetics*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000201:enzymology*; D012584:Sciatic Nerve / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic
D000110:Acetylcholinesterase; D015740:Calcitonin Gene-Related Peptide