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Requirement of dendritic Akt degradation by the ubiquitin-proteasome system for neuronal polarity.

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

SUBMITTER: Yan D

PROVIDER: S-EPMC2064237 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Requirement of dendritic Akt degradation by the ubiquitin-proteasome system for neuronal polarity.

Yan Dong D Guo Li L Wang Yizheng Y

The Journal of cell biology 20060724 3

Asymmetric distributions of activities of the protein kinases Akt and glycogen synthase kinase 3beta (GSK-3beta) are critical for the formation of neuronal polarity. However, the mechanisms underlying polarized regulation of this pathway remain unclear. In this study, we report that the instability of Akt regulated by the ubiquitin-proteasome system (UPS) is required for neuron polarity. Preferential distribution in the axons was observed for Akt but not for its target GSK-3beta. A photoactivata ...[more]

PMID: 16864652

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