title: The PRiMA-linked cholinesterase tetramers are assembled from homodimers: hybrid molecules composed of acetylcholinesterase and butyrylcholinesterase dimers are up-regulated during development of chicken brain.
abstract: Acetylcholinesterase (AChE) is anchored onto cell membranes by the transmembrane protein PRiMA (proline-rich membrane anchor) as a tetrameric globular form that is prominently expressed in vertebrate brain. In parallel, the PRiMA-linked tetrameric butyrylcholinesterase (BChE) is also found in the brain. A single type of AChE-BChE hybrid tetramer was formed in cell cultures by co-transfection of cDNAs encoding AChE(T) and BChE(T) with proline-rich attachment domain-containing proteins, PRiMA I, PRiMA II, or a fragment of ColQ having a C-terminal GPI addition signal (Q(N-GPI)). Using AChE and BChE mutants, we showed that AChE-BChE hybrids linked with PRiMA or Q(N-GPI) always consist of AChE(T) and BChE(T) homodimers. The dimer formation of AChE(T) and BChE(T) depends on the catalytic domains, and the assembly of tetramers with a proline-rich attachment domain-containing protein requires the presence of C-terminal "t-peptides" in cholinesterase subunits. Our results indicate that PRiMA- or ColQ-linked cholinesterase tetramers are assembled from AChE(T) or BChE(T) homodimers. Moreover, the PRiMA-linked AChE-BChE hybrids occur naturally in chicken brain, and their expression increases during development, suggesting that they might play a role in cholinergic neurotransmission.
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Vicky P
authors.initials: VP
authors.lastname: Chen
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Heidi Q
authors.initials: HQ
authors.lastname: Xie
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Wallace K B
authors.initials: WKB
authors.lastname: Chan
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: K Wing
authors.initials: KW
authors.lastname: Leung
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Gallant K L
authors.initials: GKL
authors.lastname: Chan
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Roy C Y
authors.initials: RCY
authors.lastname: Choi
authors.affiliation: CNRS-UMR 8197, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bon
authors.affiliation: CNRS-UMR 8197, Institut de Biologie de l'Ecole Normale Supérieure, 75005 Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Massoulié
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: botsim@ust.hk.
authors.forename: Karl W K
authors.initials: KWK
authors.lastname: Tsim
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D010455:Peptides; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase