On July 31st, Journal of Cell Biology published a report from ION entitled “Requirement of dendritic Akt degradation by ubiquitin proteasome system for neuronal polarity”. This work was done by graduate students Dong Yan and Li Guo, under the supervisoin of Dr. Yi-zheng Wang.

Our brain consists of a complex network of billions of neurons, connected to each other through intricate and precise circuitry. Although neurons are highly diverse in their morphology and function, they generally consist of a single, long axon, which sends information to downstream neurons, and multiple, complex dendrites which receive information from other neurons. The establishment of axonal-dendritic polarity is an essential step in neuronal development; yet, much remains to be determined about its molecular mechanisms. Recent work from the Laboratory of Neural Signal Transduction headed by Dr. Yi-zheng Wang demonstrated a novel mechanism in the establishment of neuron polarity.

Asymmetric distributions of kinase activity of the protein kinases Akt and glycogen synthase kinase 3β (GSK-3β) are known to be critical to the formation of neuronal polarity. However, the mechanisms underlying polarized regulation of this pathway remain unclear. Their research showed that the degradation of Akt as regulated by the ubiquitin-proteasome system (UPS) is required for the establishment of neuron polarity. Preferential distribution in axons was observed for Akt, but not for its target, GSK-3β. A photoactivatable GFP fused to Akt revealed preferential degradation of Akt in dendrites. Akt, but not p110 or GSK-3β, was ubiquitinated. Suppressing the UPS led to symmetric distribution of Akt and the formation of multiple axons. These results indicate that local protein degradation mediated by the UPS is important for determining neuronal polarity.