A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation.
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.
Yang
Yue
Y
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Kim
Albert H
AH
Yamada
Tomoko
T
Wu
Bei
B
Bilimoria
Parizad M
PM
Ikeuchi
Yoshiho
Y
de la Iglesia
Núria
N
Shen
Jie
J
Bonni
Azad
A
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*
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