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Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin.

Wang X, Kibschull M, Laue MM, Lichte B, Petrasch-Parwez E, Kilimann MW - J. Cell Biol. (1999)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.

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.

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Sequence alignment of mouse aczonin (mACZ), chicken aczonin (cACZ), and rat Bassoon (Bsn). The long splicing variants are shown (mouse, L; chicken, XL), and the position at mouse codon 4829 is indicated by an asterisk where the QQLRIQP sequence can instead be followed by the short SKRRK COOH terminus. Overlining beginning at mouse codon 430 marks three 10-mer repeat units deleted in some mouse cDNAs. The chicken sequence is incomplete for the ∼80 NH2-terminal codons. Upstream of the putative start codon, the mouse cDNA contig continues for 304 nucleotides of GC-rich sequence with no in-frame stop codon. Additional rescreenings did not yield sequences reaching further upstream. Between aczonin and Bassoon, the first nine codons are synonymous, whereas the upstream cDNA sequences are completely dissimilar, also suggesting that the codon assumed here as methionine 1 is the true start codon. Specific sequence motifs (see Fig. 2) are framed by arrowheads above the mouse sequence (except the zinc finger and polyproline motifs that are self-evident) and designated at the right margin. The rat Bassoon sequence is taken from tom Dieck et al. 1998. EMBL/GenBank/DDBJ sequence database accession numbers are Y19185-6 (mouse aczonin-L and S), Y19187 (chicken aczonin-XL), and Y19188 (partial human aczonin; data not shown).
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Figure 1: Sequence alignment of mouse aczonin (mACZ), chicken aczonin (cACZ), and rat Bassoon (Bsn). The long splicing variants are shown (mouse, L; chicken, XL), and the position at mouse codon 4829 is indicated by an asterisk where the QQLRIQP sequence can instead be followed by the short SKRRK COOH terminus. Overlining beginning at mouse codon 430 marks three 10-mer repeat units deleted in some mouse cDNAs. The chicken sequence is incomplete for the ∼80 NH2-terminal codons. Upstream of the putative start codon, the mouse cDNA contig continues for 304 nucleotides of GC-rich sequence with no in-frame stop codon. Additional rescreenings did not yield sequences reaching further upstream. Between aczonin and Bassoon, the first nine codons are synonymous, whereas the upstream cDNA sequences are completely dissimilar, also suggesting that the codon assumed here as methionine 1 is the true start codon. Specific sequence motifs (see Fig. 2) are framed by arrowheads above the mouse sequence (except the zinc finger and polyproline motifs that are self-evident) and designated at the right margin. The rat Bassoon sequence is taken from tom Dieck et al. 1998. EMBL/GenBank/DDBJ sequence database accession numbers are Y19185-6 (mouse aczonin-L and S), Y19187 (chicken aczonin-XL), and Y19188 (partial human aczonin; data not shown).

Mentions: Aczonin was identified as a new molecular constituent of neuronal synapses by immunoscreening a brain cDNA expression library with antisera raised against synaptic plasma membranes (Lichte et al. 1992). An alignment of the cDNA-deduced mouse and chicken aczonin sequences with Bassoon is presented in Fig. 1, and an overview of the regional organization of the aczonin sequence and its similarities with Bassoon and Rim is given in Fig. 2. The longest splicing variant of mouse aczonin is predicted to be a 550-kD hydrophilic polypeptide of balanced charge (pI 6.4) featuring two mutually homologous pairs of Cys4 zinc fingers in the NH2-terminal region, a polyproline stretch in the middle (22 uninterrupted proline residues in the mouse and 11 in chicken), and a PDZ domain and two C2 motifs in the COOH-terminal region.


Aczonin, a 550-kD putative scaffolding protein of presynaptic active zones, shares homology regions with Rim and Bassoon and binds profilin.

Wang X, Kibschull M, Laue MM, Lichte B, Petrasch-Parwez E, Kilimann MW - J. Cell Biol. (1999)

Sequence alignment of mouse aczonin (mACZ), chicken aczonin (cACZ), and rat Bassoon (Bsn). The long splicing variants are shown (mouse, L; chicken, XL), and the position at mouse codon 4829 is indicated by an asterisk where the QQLRIQP sequence can instead be followed by the short SKRRK COOH terminus. Overlining beginning at mouse codon 430 marks three 10-mer repeat units deleted in some mouse cDNAs. The chicken sequence is incomplete for the ∼80 NH2-terminal codons. Upstream of the putative start codon, the mouse cDNA contig continues for 304 nucleotides of GC-rich sequence with no in-frame stop codon. Additional rescreenings did not yield sequences reaching further upstream. Between aczonin and Bassoon, the first nine codons are synonymous, whereas the upstream cDNA sequences are completely dissimilar, also suggesting that the codon assumed here as methionine 1 is the true start codon. Specific sequence motifs (see Fig. 2) are framed by arrowheads above the mouse sequence (except the zinc finger and polyproline motifs that are self-evident) and designated at the right margin. The rat Bassoon sequence is taken from tom Dieck et al. 1998. EMBL/GenBank/DDBJ sequence database accession numbers are Y19185-6 (mouse aczonin-L and S), Y19187 (chicken aczonin-XL), and Y19188 (partial human aczonin; data not shown).
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Figure 1: Sequence alignment of mouse aczonin (mACZ), chicken aczonin (cACZ), and rat Bassoon (Bsn). The long splicing variants are shown (mouse, L; chicken, XL), and the position at mouse codon 4829 is indicated by an asterisk where the QQLRIQP sequence can instead be followed by the short SKRRK COOH terminus. Overlining beginning at mouse codon 430 marks three 10-mer repeat units deleted in some mouse cDNAs. The chicken sequence is incomplete for the ∼80 NH2-terminal codons. Upstream of the putative start codon, the mouse cDNA contig continues for 304 nucleotides of GC-rich sequence with no in-frame stop codon. Additional rescreenings did not yield sequences reaching further upstream. Between aczonin and Bassoon, the first nine codons are synonymous, whereas the upstream cDNA sequences are completely dissimilar, also suggesting that the codon assumed here as methionine 1 is the true start codon. Specific sequence motifs (see Fig. 2) are framed by arrowheads above the mouse sequence (except the zinc finger and polyproline motifs that are self-evident) and designated at the right margin. The rat Bassoon sequence is taken from tom Dieck et al. 1998. EMBL/GenBank/DDBJ sequence database accession numbers are Y19185-6 (mouse aczonin-L and S), Y19187 (chicken aczonin-XL), and Y19188 (partial human aczonin; data not shown).
Mentions: Aczonin was identified as a new molecular constituent of neuronal synapses by immunoscreening a brain cDNA expression library with antisera raised against synaptic plasma membranes (Lichte et al. 1992). An alignment of the cDNA-deduced mouse and chicken aczonin sequences with Bassoon is presented in Fig. 1, and an overview of the regional organization of the aczonin sequence and its similarities with Bassoon and Rim is given in Fig. 2. The longest splicing variant of mouse aczonin is predicted to be a 550-kD hydrophilic polypeptide of balanced charge (pI 6.4) featuring two mutually homologous pairs of Cys4 zinc fingers in the NH2-terminal region, a polyproline stretch in the middle (22 uninterrupted proline residues in the mouse and 11 in chicken), and a PDZ domain and two C2 motifs in the COOH-terminal region.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.

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.

Show MeSH
Related in: MedlinePlus