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* |
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Authors: | Vicky P Chen Heidi Q Xie Wallace K B Chan K Wing Leung Gallant K L Chan Roy C Y Choi Suzanne Bon Jean Massoulié Karl W K Tsim |
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Institution: | From the ‡Department of Biology and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China and ;§CNRS-UMR 8197, Institut de Biologie de l''Ecole Normale Supérieure, 75005 Paris, France |
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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 AChET and BChET with proline-rich attachment domain-containing proteins, PRiMA I, PRiMA II, or a fragment of ColQ having a C-terminal GPI addition signal (QN-GPI). Using AChE and BChE mutants, we showed that AChE-BChE hybrids linked with PRiMA or QN-GPI always consist of AChET and BChET homodimers. The dimer formation of AChET and BChET 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 AChET or BChET 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. |
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Keywords: | Acetylcholinesterase Brain Multifunctional Enzymes Neurodevelopment Protein Assembly Butyrylcholinesterase Cholinergic Synapse Hybrid Tetramer PRiMA Protein Assembly |
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