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Science 326 (5952): 575-578

Copyright © 2009 by the American Association for the Advancement of Science

A Cdc20-APC Ubiquitin Signaling Pathway Regulates Presynaptic Differentiation

Yue Yang,1,2 Albert H. Kim,1,3 Tomoko Yamada,1 Bei Wu,4 Parizad M. Bilimoria,1,2 Yoshiho Ikeuchi,1 Núria de la Iglesia,1 Jie Shen,2,4 Azad Bonni1,2,*

Abstract: 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.

1 Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
2 Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
3 Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA 02115, USA.
4 Center for Neurologic Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: azad_bonni{at}hms.harvard.edu

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