Published online 8 August 2005. doi:10.1083/jcb1704iti2
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 4, 510-510
Replication complexes in neuronal morphology
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Dendritic branching is reduced in cells missing Orc3 (right).
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A replication initiation complex finds things to do in neurons that no longer replicate, as shown by Huang et al. (page 527). The origin recognition complex (ORC), the authors show, allows dendrites to expand their territory and make new synaptic connections.
Adult neurons are postmitotic; they thus have little or no need for DNA replication. Yet the authors noticed that ORC subunits were expressed in the mouse brain. Further, the proteins were found in dendrites rather than in the nucleus, where their typical function is performed. Knock-down studies revealed that neurons require ORC for dendritic branching and spine formation, which are the morphological mechanisms of synaptic plasticity in adult neurons.
ORC-lacking dendrites were unable to send out filopodia, which initiate both branches and spines. The actin-bundling proteins Mena and VASP, which are necessary for filopodia formation, failed to cluster periodically at the dendritic membrane, as they did in wild-type dendrites. How ORC controls the localization of the actin organizers is unclear. The group found that ORC localized to the plasma membrane, where it might regulate Rho activity, for instance.
The results are not the first connection between cell cycle components and neuronal development. Others have shown, for instance, that the anaphase-promoting complex is also needed for synaptic maturation. The similarities between cell division and neurons might stem from the periodic aspects of both cell cycle progression and synaptic activation. Now the authors would like to find a CDK-like activity that controls various neuronal developmental processes in response to depolarization, for example. CDK5 is one possibility, as it is expressed in postmitotic neurons. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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The origin recognition core complex regulates dendrite and spine development in postmitotic neurons
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