TY - JOUR
T1 - A Centrosomal Cdc20-APC Pathway Controls Dendrite Morphogenesis in Postmitotic Neurons
AU - Kim, Albert H.
AU - Puram, Sidharth V.
AU - Bilimoria, Parizad M.
AU - Ikeuchi, Yoshiho
AU - Keough, Samantha
AU - Wong, Michael
AU - Rowitch, David
AU - Bonni, Azad
N1 - Funding Information:
Supported by National Institutes of Health grants NS051255 and NS41021 (A.B.), a Ruth L. Kirschstein National Research Service Award research fellowship, the National Cancer Institute, and Brain Science Foundation grant (A.H.K.), the Albert J Ryan Foundation (P.B.), and a Human Frontier Science Program Long-Term Fellowship (Y.I.). We thank members of the Bonni laboratory for helpful discussions and critical reading of the manuscript.
PY - 2009/1/23
Y1 - 2009/1/23
N2 - 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.
AB - 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.
KW - MOLNEURO
UR - http://www.scopus.com/inward/record.url?scp=58249091452&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2008.11.050
DO - 10.1016/j.cell.2008.11.050
M3 - Article
C2 - 19167333
AN - SCOPUS:58249091452
SN - 0092-8674
VL - 136
SP - 322
EP - 336
JO - Cell
JF - Cell
IS - 2
ER -