title: A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation.
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.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kim
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada
authors.forename: Bei
authors.initials: B
authors.lastname: Wu
authors.forename: Parizad M
authors.initials: PM
authors.lastname: Bilimoria
authors.forename: Yoshiho
authors.initials: Y
authors.lastname: Ikeuchi
authors.forename: Núria
authors.initials: N
authors.lastname: de la Iglesia
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Azad
authors.initials: A
authors.lastname: Bonni
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002525:Cerebellar Cortex / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D050505:Mutant Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D064173:Anaphase-Promoting Complex-Cyclosome; D051792:Basic Helix-Loop-Helix Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016704:Synapsins; D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; C577494:Cdc20 protein, rat; C490924:Neurod2 protein, rat; C095993:complexin II