Abstract
Neurotransmitter exocytosis is restricted to the active zone, a specialized area of the presynaptic plasma membrane. We report the identification and initial characterization of aczonin, a neuron-specific 550-kD protein concentrated at the presynaptic active zone and associated with a detergent-resistant cytoskeletal subcellular fraction. Analysis of the amino acid sequences of chicken and mouse aczonin indicates an organization into multiple domains, including two pairs of Cys(4) zinc fingers, a polyproline tract, and a PDZ domain and two C2 domains near the COOH terminus. The second C2 domain is subject to differential splicing. Aczonin binds profilin, an actin-binding protein implicated in actin cytoskeletal dynamics. Large parts of aczonin, including the zinc finger, PDZ, and C2 domains, are homologous to Rim or to Bassoon, two other proteins concentrated in presynaptic active zones. We propose that aczonin is a scaffolding protein involved in the organization of the molecular architecture of synaptic active zones and in the orchestration of neurotransmitter vesicle trafficking.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Brain / cytology
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Brain / drug effects
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Brain / metabolism
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Carrier Proteins / chemistry*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line
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Cell Membrane / metabolism
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Chickens
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Contractile Proteins*
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Cytoskeletal Proteins / chemistry*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Cytoskeleton / drug effects
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Cytoskeleton / metabolism
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GTP-Binding Proteins*
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Humans
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Mice
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Microfilament Proteins / metabolism*
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Molecular Sequence Data
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Molecular Weight
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Nerve Tissue Proteins / chemistry*
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Neuropeptides
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Organ Specificity
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Peptides / chemistry
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Peptides / genetics
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Peptides / metabolism
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Presynaptic Terminals / metabolism*
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Profilins
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Rats
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Sequence Homology, Amino Acid
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Zinc Fingers
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rab3A GTP-Binding Protein / metabolism
Substances
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BSN protein, human
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Bsn protein, mouse
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Bsn protein, rat
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Carrier Proteins
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Contractile Proteins
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Cytoskeletal Proteins
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Microfilament Proteins
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Nerve Tissue Proteins
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Neuropeptides
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PCLO protein, human
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PFN1 protein, human
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Pclo protein, mouse
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Pclo protein, rat
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Peptides
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Pfn1 protein, mouse
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Pfn1 protein, rat
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Profilins
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RIMS1 protein, human
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RNA, Messenger
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Rim protein, mammalian
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Rims1 protein, mouse
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Rims1 protein, rat
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polyproline
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GTP-Binding Proteins
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rab3A GTP-Binding Protein
Associated data
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GENBANK/Y19185
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GENBANK/Y19186
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GENBANK/Y19187
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GENBANK/Y19188