Details

Autor(en) / Beteiligte

• Ma, Huan
• Groth, Rachel D
• Cohen, Samuel M
• Emery, John F
• Li, Boxing
• Hoedt, Esthelle
• Zhang, Guoan
• Neubert, Thomas A
• Tsien, Richard W

Titel

gamma CaMKII Shuttles Ca super(2+)/CaM to the Nucleus to Trigger CREB Phosphorylation and Gene Expression

Ist Teil von

• Cell, 2014-10, Vol.159 (2), p.281-294

Erscheinungsjahr

2014

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Activity-dependent CREB phosphorylation and gene expression are critical for long-term neuronal plasticity. Local signaling at Ca sub(V)1 channels triggers these events, but how information is relayed onward to the nucleus remains unclear. Here, we report a mechanism that mediates long-distance communication within cells: a shuttle that transports Ca super(2+)/calmodulin from the surface membrane to the nucleus. We show that the shuttle protein is gamma CaMKII, its phosphorylation at Thr287 by beta CaMKII protects the Ca super(2+)/CaM signal, and CaN triggers its nuclear translocation. Both beta CaMKII and CaN act in close proximity to Ca sub(V)1 channels, supporting their dominance, whereas gamma CaMKII operates as a carrier, not as a kinase. Upon arrival within the nucleus, Ca super(2+)/CaM activates CaMKK and its substrate CaMKIV, the CREB kinase. This mechanism resolves long-standing puzzles about CaM/CaMK-dependent signaling to the nucleus. The significance of the mechanism is emphasized by dysregulation of Ca sub(V)1, gamma CaMKII, beta CaMKII, and CaN in multiple neuropsychiatric disorders.