ABSTRACT
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.
Subject(s)
Centrosome/metabolism , Cerebellar Cortex/cytology , Dendrites/metabolism , Neurons/cytology , Signal Transduction , Anaphase-Promoting Complex-Cyclosome , Animals , Cdc20 Proteins , Cell Cycle Proteins/metabolism , In Vitro Techniques , Inhibitor of Differentiation Protein 1/metabolism , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Ubiquitin-Protein Ligase Complexes/metabolismABSTRACT
There is good evidence that interference with the mesolimbic dopamine (DA) system results in impaired maternal responding in postpartum female rats. However, whether activation of the mesolimbic DA system is capable of promoting maternal behavior has not been investigated. This study examined whether increasing DA activity in various brain regions of pregnancy-terminated, naive female rats would stimulate the onset of maternal behavior. Experiments 1 and 2 examined the effects of microinjection of various doses (0, 0.2, or 0.5 microg/0.5 microl/side) of a D1 DA receptor agonist, SKF 38393, or a D2 DA receptor agonist, quinpirole, into the nucleus accumbens (NA) on latency to show full maternal behavior, and Experiment 3 determined the effects of SKF 38393 injection into a control site. Finally, because the medial preoptic area (MPOA) is also important for maternal behavior, receives DA input, and expresses DA receptors, the authors examined whether microinjection of SKF 38393 into MPOA was capable of stimulating the onset of maternal behavior. Results indicated that microinjection of SKF 38393 into either the NA or the MPOA facilitates maternal responding in pregnancy-terminated rats.
