TORC1 Regulates Activity-Dependent CREB-Target Gene Transcription and Dendritic Growth of Developing Cortical Neurons

• DOI: 10.1523/jneurosci.2296-08.2009
• Publication Date: 2009-02-25T18:34:19Z
• Authors: Shuai Li; Chi Zhang; Hiroshi Takemori; Yang Zhou; Zhi-Qi Xiong
• Keywords: Cortical neurons; Transcription

CREB-target gene transcription during neuronal excitation is important for many aspects of development and function, including dendrite morphogenesis. However, the signaling events that regulate cAMP response element-binding protein (CREB)-mediated dendritic are not well understood. Herein we report CREB coactivator TORC1 (transducer regulated 1) required activity-dependent expression growth in developing cortical neurons. Ca(2+) influx via voltage-gated calcium channels induced dephosphorylation translocation into nucleus a calcineurin-dependent manner. Nuclear accumulation initiated genes, salt-inducible kinase 1 (SIK1). In persistent depolarization, de novo SIK1 turn promoted phosphorylation consequent depletion nucleus-localized TORC1. induction thus appears to act as negative feedback signal prevents CREB/TORC1-dependent face long-lasting activity. Overexpressing wild type basal activity-induced growth, whereas expressing dominant-negative form or downregulating inhibited vitro vivo. Together, these results suggest neurons relies on transient TORC1-mediated transcription.