A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons.
The ubiquitin ligase anaphase-promoting complex (APC) recruits the coactivator Cdc20 to drive mitosis in cycling cells. However, the nonmitotic functions of Cdc20-APC have remained unexplored. We report that Cdc20-APC plays an essential role in dendrite morphogenesis in postmitotic neurons. Knockdown of Cdc20 in cerebellar slices and in postnatal rats in vivo profoundly impairs the formation of granule neuron dendrite arbors in the cerebellar cortex. Remarkably, Cdc20 is enriched at the centrosome in neurons, and the centrosomal localization is critical for Cdc20-dependent dendrite development. We also find that the centrosome-associated protein histone deacetylase 6 (HDAC6) promotes the polyubiquitination of Cdc20, stimulates the activity of centrosomal Cdc20-APC, and drives the differentiation of dendrites. These findings define a postmitotic function for Cdc20-APC in the morphogenesis of dendrites in the mammalian brain. The identification of a centrosomal Cdc20-APC ubiquitin signaling pathway holds important implications for diverse biological processes, including neuronal connectivity and plasticity.
Kim
Albert H
AH
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
Puram
Sidharth V
SV
Bilimoria
Parizad M
PM
Ikeuchi
Yoshiho
Y
Keough
Samantha
S
Wong
Michael
M
Rowitch
David
D
Bonni
Azad
A
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002525:Cerebellar Cortex / Q000166:cytology*; D003712:Dendrites / Q000378:metabolism*; D066298:In Vitro Techniques; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
D064199:Cdc20 Proteins; C577494:Cdc20 protein, rat; D018797:Cell Cycle Proteins; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome