Transcriptional control of different acetylcholinesterase subunits in formation and maintenance of vertebrate neuromuscular junctions.
Acetylcholinesterase (AChE; EC 3.1.1.7) is a highly polymorphic enzyme (Massoulié, 2002). Asingle ACHE gene produces several types of catalytic subunits by alternative splicing, but a single splice variant, called type T (AChET), is expressed in adult mammalian muscle and brain. Catalytic subunits of AChET produce amphiphilic monomers and dimers, nonamphiphilic homotetramers, as well as heteromeric associations with anchoring proteins, ColQ (collagenous subunit) and PRiMA (proline-rich membrane anchor), which allow their functional localization in cholinergic synapses (Massoulié, 2002). ColQ characterizes the collagen-tailed forms (Aforms) of AChE and butyrylcholinesterase (BChE), which are localized in the basal lamina at neuromuscular junctions (NMJs) of vertebrates (Krejci et al., 1999); in these molecules (A4, A8, A12), one, two, or three tetramers of catalytic subunits are disulfide-linked to the strands of a triple helix of ColQ collagen. The cDNAs encoding ColQ, which have two transcripts, have been cloned: ColQ-1a predominantly in fast-twitch muscle, and ColQ-1 predominantly in slow-twitch muscle. The tetrameric globular (G4) form of AChE is characterized by linkage to PRiMA. PRiMAcDNA encodes a single-pass approximately 20-kDa type-I transmembrane protein and, similar to that of ColQ, contains a short PRAD (proline-rich attachment domain) that is able to organize AChE catalytic subunits into tetramers and anchor the enzyme at the surface of neuron and muscle (Massoulié, 2002).
Tsim
Karl W K
KW
Department of Biology, The Hong Kong University of Science and Technology, Hong Kong SAR, China. botsim@ust.hk
Xie
Heidi Q H
HQ
Ting
Annie K L
AK
Siow
Nina L
NL
Ling
Karen K Y
KK
Kong
Ling W
LW
D000110:Acetylcholinesterase / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D002642:Chick Embryo; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D014644:Genetic Variation; D007700:Kinetics; D008322:Mammals; D009469:Neuromuscular Junction / Q000201:enzymology*; D021122:Protein Subunits / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014714:Vertebrates
D017931:DNA Primers; D021122:Protein Subunits; D000110:Acetylcholinesterase