| First Author | Ninkina N | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 53 | Pages | 44471-7 |
| PubMed ID | 23129765 | Mgi Jnum | J:193755 |
| Mgi Id | MGI:5469524 | Doi | 10.1074/jbc.M112.422402 |
| Citation | Ninkina N, et al. (2012) Contrasting effects of alpha-synuclein and gamma-synuclein on the phenotype of cysteine string protein alpha (CSPalpha) null mutant mice suggest distinct function of these proteins in neuronal synapses. J Biol Chem 287(53):44471-7 |
| abstractText | 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 alpha (CSPalpha) 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, alpha-synuclein, also potentiates SNARE complex formation, and its overexpression rescues the phenotype of CSPalpha null mutant mice, although these two proteins use different mechanisms to achieve this effect. alpha-Synuclein is a member of a family of three related proteins whose structural similarity suggests functional redundancy. Here, we assessed whether gamma-synuclein shares the ability of alpha-synuclein to bind synaptic vesicles and ameliorate neurodegeneration caused by CSPalpha 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 gamma-synuclein was not able to interact with synaptobrevin-2/VAMP2. Consequently, overexpression of gamma-synuclein did not have any noticeable effect on the phenotype of CSPalpha null mutant mice. Our data suggest that the functions of alpha- and gamma-synucleins in presynaptic terminals are not fully redundant. |
