Journal
SCIENCE
Volume 326, Issue 5952, Pages 575-578Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1177087
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Funding
- NIH [NS051255, NS041021]
- NSF
- Lefler Fellowship
- Ryan Foundation
- National Research Service Award Research Training
- National Cancer Institute, and Brain Science Foundation
- Japan Society for the Promotion of Science
- Human Frontier Science Program
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Presynaptic axonal differentiation is essential for synapse formation and the establishment of neuronal circuits. However, the mechanisms that coordinate presynaptic development in the brain are largely unknown. We found that the major mitotic E3 ubiquitin ligase Cdc20-anaphase promoting complex (Cdc20-APC) regulates presynaptic differentiation in primary postmitotic mammalian neurons and in the rat cerebellar cortex. Cdc20-APC triggered the degradation of the transcription factor NeuroD2 and thereby promoted presynaptic differentiation. The NeuroD2 target gene encoding Complexin II, which acts locally at presynaptic sites, mediated the ability of NeuroD2 to suppress presynaptic differentiation. Thus, our findings define a Cdc20-APC ubiquitin signaling pathway that governs presynaptic development, which holds important implications for neuronal connectivity and plasticity in the brain.
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