Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses.
In neuronal synapses, neurotransmitter-loaded vesicles fuse with presynaptic plasma membrane in a complex sequence of tightly regulated events. The assembly of specialized SNARE complexes plays a pivotal role in this process. The function of the chaperone cysteine string protein α (CSPα) is importan...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797087923376488448 |
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| author | Ninkina, N Peters, O Connor-Robson, N Lytkina, O Sharfeddin, E Buchman, V |
| author_facet | Ninkina, N Peters, O Connor-Robson, N Lytkina, O Sharfeddin, E Buchman, V |
| author_sort | Ninkina, N |
| collection | OXFORD |
| description | In neuronal synapses, neurotransmitter-loaded vesicles fuse with presynaptic plasma membrane in a complex sequence of tightly regulated events. The assembly of specialized SNARE complexes plays a pivotal role in this process. The function of the chaperone cysteine string protein α (CSPα) is important for synaptic SNARE complex formation, and mice lacking this protein develop severe synaptic dysfunction and neurodegeneration that lead to their death within 3 months after birth. Another presynaptic protein, α-synuclein, also potentiates SNARE complex formation, and its overexpression rescues the phenotype of CSPα null mutant mice, although these two proteins use different mechanisms to achieve this effect. α-Synuclein is a member of a family of three related proteins whose structural similarity suggests functional redundancy. Here, we assessed whether γ-synuclein shares the ability of α-synuclein to bind synaptic vesicles and ameliorate neurodegeneration caused by CSPα deficiency in vivo. Although the N-terminal lipid-binding domains of the two synucleins showed similar affinity for purified synaptic vesicles, the C-terminal domain of γ-synuclein was not able to interact with synaptobrevin-2/VAMP2. Consequently, overexpression of γ-synuclein did not have any noticeable effect on the phenotype of CSPα null mutant mice. Our data suggest that the functions of α- and γ-synucleins in presynaptic terminals are not fully redundant. |
| first_indexed | 2024-03-07T02:42:29Z |
| format | Journal article |
| id | oxford-uuid:aaed4fa3-4cb8-43bd-82a9-1dfa4169c323 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:42:29Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:aaed4fa3-4cb8-43bd-82a9-1dfa4169c3232022-03-27T03:18:27ZContrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:aaed4fa3-4cb8-43bd-82a9-1dfa4169c323EnglishSymplectic Elements at Oxford2012Ninkina, NPeters, OConnor-Robson, NLytkina, OSharfeddin, EBuchman, VIn neuronal synapses, neurotransmitter-loaded vesicles fuse with presynaptic plasma membrane in a complex sequence of tightly regulated events. The assembly of specialized SNARE complexes plays a pivotal role in this process. The function of the chaperone cysteine string protein α (CSPα) is important for synaptic SNARE complex formation, and mice lacking this protein develop severe synaptic dysfunction and neurodegeneration that lead to their death within 3 months after birth. Another presynaptic protein, α-synuclein, also potentiates SNARE complex formation, and its overexpression rescues the phenotype of CSPα null mutant mice, although these two proteins use different mechanisms to achieve this effect. α-Synuclein is a member of a family of three related proteins whose structural similarity suggests functional redundancy. Here, we assessed whether γ-synuclein shares the ability of α-synuclein to bind synaptic vesicles and ameliorate neurodegeneration caused by CSPα deficiency in vivo. Although the N-terminal lipid-binding domains of the two synucleins showed similar affinity for purified synaptic vesicles, the C-terminal domain of γ-synuclein was not able to interact with synaptobrevin-2/VAMP2. Consequently, overexpression of γ-synuclein did not have any noticeable effect on the phenotype of CSPα null mutant mice. Our data suggest that the functions of α- and γ-synucleins in presynaptic terminals are not fully redundant. |
| spellingShingle | Ninkina, N Peters, O Connor-Robson, N Lytkina, O Sharfeddin, E Buchman, V Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title | Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title_full | Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title_fullStr | Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title_full_unstemmed | Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title_short | Contrasting effects of α-synuclein and γ-synuclein on the phenotype of cysteine string protein α (CSPα) null mutant mice suggest distinct function of these proteins in neuronal synapses. |
| title_sort | contrasting effects of α synuclein and γ synuclein on the phenotype of cysteine string protein α cspα null mutant mice suggest distinct function of these proteins in neuronal synapses |
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