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An optogenetic system for interrogating the temporal dynamics of Akt.

ABSTRACT: The dynamic activity of the serine/threonine kinase Akt is crucial for the regulation of diverse cellular functions, but the precise spatiotemporal control of its activity remains a critical issue. Herein, we present a photo-activatable Akt (PA-Akt) system based on a light-inducible protein interaction module of Arabidopsis thaliana cryptochrome2 (CRY2) and CIB1. Akt fused to CRY2phr, which is a minimal light sensitive domain of CRY2 (CRY2-Akt), is reversibly activated by light illumination in several minutes within a physiological dynamic range and specifically regulates downstream molecules and inducible biological functions. We have generated a computational model of CRY2-Akt activation that allows us to use PA-Akt to control the activity quantitatively. The system provides evidence that the temporal patterns of Akt activity are crucial for generating one of the downstream functions of the Akt-FoxO pathway; the expression of a key gene involved in muscle atrophy (Atrogin-1). The use of an optical module with computational modeling represents a general framework for interrogating the temporal dynamics of biomolecules by predictive manipulation of optogenetic modules.

SUBMITTER: Katsura Y

PROVIDER: S-EPMC4589684 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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An optogenetic system for interrogating the temporal dynamics of Akt.

Katsura Yoshihiro Y Kubota Hiroyuki H Kunida Katsuyuki K Kanno Akira A Kuroda Shinya S Ozawa Takeaki T

Scientific reports 20151001

The dynamic activity of the serine/threonine kinase Akt is crucial for the regulation of diverse cellular functions, but the precise spatiotemporal control of its activity remains a critical issue. Herein, we present a photo-activatable Akt (PA-Akt) system based on a light-inducible protein interaction module of Arabidopsis thaliana cryptochrome2 (CRY2) and CIB1. Akt fused to CRY2phr, which is a minimal light sensitive domain of CRY2 (CRY2-Akt), is reversibly activated by light illumination in s ...[more]

PMID: 26423353

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An optogenetic system for interrogating the temporal dynamics of Akt.

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An optogenetic system for interrogating the temporal dynamics of Akt.

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