• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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.

Pubmed ID: 19167333

Authors

  • Kim AH
  • Puram SV
  • Bilimoria PM
  • Ikeuchi Y
  • Keough S
  • Wong M
  • Rowitch D
  • Bonni A

Journal

Cell

Publication Data

January 23, 2009

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS051255
  • Agency: NINDS NIH HHS, Id: NS41021
  • Agency: NINDS NIH HHS, Id: R01 NS041021
  • Agency: NINDS NIH HHS, Id: R01 NS041021-06
  • Agency: NINDS NIH HHS, Id: R01 NS041021-07
  • Agency: NINDS NIH HHS, Id: R01 NS041021-08
  • Agency: NINDS NIH HHS, Id: R01 NS051255
  • Agency: NINDS NIH HHS, Id: R01 NS051255-02
  • Agency: NINDS NIH HHS, Id: R01 NS051255-03
  • Agency: NINDS NIH HHS, Id: R01 NS051255-04
  • Agency: NIGMS NIH HHS, Id: T32 GM007753

Mesh Terms

  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • Centrosome
  • Cerebellar Cortex
  • Dendrites
  • In Vitro Techniques
  • Inhibitor of Differentiation Protein 1
  • Neurons
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Ubiquitin-Protein Ligase Complexes