title: PRiMA directs a restricted localization of tetrameric AChE at synapses.
abstract: Acetylcholinesterase (AChE), a highly polymorphic enzyme with various splicing variants and molecular isoforms, plays an essential role in the cholinergic neurotransmission by hydrolyzing acetylcholine into choline and acetate. The AChE(T) variant is expressed in the brain and muscle: this subunit forms non-amphiphilic tetramers with a collagen tail (ColQ) as asymmetric AChE (A(12) AChE) in muscle, and amphiphilic tetramers with a proline-rich membrane anchor (PRiMA) as globular AChE (G(4) AChE) in the brain and muscle. During the brain development, the expression of amphiphilic G(4) AChE is up regulated and becomes the predominant form of AChE there. This up-regulation of G(4) AChE can be attributed to the increased expressions of both AChE(T) and PRiMA. A significant portion of this membrane-bound G(4) AChE is localized at the membrane rafts of the cell membranes derived from the brain. This raft association could be directed by PRiMA via its CRAC (cholesterol recognition/interaction amino acid consensus) motif and C-terminus. In cultured cortical neurons and muscles, the PRiMA-linked AChE was clustered and partially co-localized with synaptic proteins. The restricted localizations suggest that the raft association of PRiMA-linked AChE could account for its synaptic localization and function.
authors.affiliation: Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Clear Water Bay Road, Hong Kong, China.
authors.forename: Heidi Q
authors.initials: HQ
authors.lastname: Xie
authors.forename: K Wing
authors.initials: KW
authors.lastname: Leung
authors.forename: Vicky P
authors.initials: VP
authors.lastname: Chen
authors.forename: Gallant K L
authors.initials: GK
authors.lastname: Chan
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Xu
authors.forename: Ava J Y
authors.initials: AJ
authors.lastname: Guo
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Zhu
authors.forename: Ken Y Z
authors.initials: KY
authors.lastname: Zheng
authors.forename: Cathy W
authors.initials: CW
authors.lastname: Bi
authors.forename: Janis Y X
authors.initials: JY
authors.lastname: Zhan
authors.forename: Wallace K P
authors.initials: WK
authors.lastname: Chan
authors.forename: Roy C Y
authors.initials: RC
authors.lastname: Choi
authors.forename: Karl W K
authors.initials: KW
authors.lastname: Tsim
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D013569:Synapses / Q000201:enzymology / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000110:Acetylcholinesterase