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Deisseroth, K., Heist, E. K. & Tsien, R. W. Calmodulin translocation to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392, 198-202

Department of Molecular and Cellular Physiology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, California 94305-5426, USA.
Nature (Impact Factor: 42.35). 03/1998; 392(6672):198-202. DOI: 10.1038/32448
Source: PubMed

ABSTRACT Activation of the transcription factor CREB is thought to be important in the formation of long-term memory in several animal species. The phosphorylation of a serine residue at position 133 of CREB is critical for activation of CREB. This phosphorylation is rapid when driven by brief synaptic activity in hippocampal neurons. It is initiated by a highly local, rise in calcium ion concentrations near the cell membrane, but culminates in the activation of a specific calmodulin-dependent kinase known as CaMK IV, which is constitutively present in the neuronal nucleus. It is unclear how the signal is conveyed from the synapse to the nucleus. We show here that brief bursts of activity cause a swift (approximately 1 min) translocation of calmodulin from the cytoplasm to the nucleus, and that this translocation is important for the rapid phosphorylation of CREB. Certain Ca2+ entry systems (L-type Ca2+ channels and NMDA receptors) are able to cause mobilization of calmodulin, whereas others (N- and P/Q-type Ca2+ channels) are not. This translocation of calmodulin provides a form of cellular communication that combines the specificity of local Ca2+ signalling with the ability to produce action at a distance.

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    • "L-type calcium channels (LTCCs), a long-opening high-voltage-gated calcium channel , are known to play an important role in triggering intracellular cascades related to synaptic plasticity (Deisseroth et al., 1998; Mermelstein et al., 2000) and in Hebbian synaptic plasticity at glutamatergic synapses (Bauer et al., 2002; Grover and Teyler, 1990, 1992; Weisskopf et al., 1999). We have investigated the potential contribution of these channels to early odor preference learning (Jerome et al., 2012). "
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    • "These Ca 2+ influxes might influence gene expression by several mechanisms. Ca 2+ can diffuse to the nucleus and activate nuclear calcium-dependent transcription factors and coregulators (Hardingham et al., 2001) or Ca 2+ can activate calcium-dependent signaling proteins around the mouth of the channel, which propagate the signal to the nucleus (Deisseroth et al., 1998; Dolmetsch et al., 2001). Another mechanism was recently observed in neurons (Gomez-Ospina et al., 2006) and cardiac myocytes (Schroder et al., 2009). "
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    • "of Nod factor. From this we infer that the introduction of Nod factors to the system also brings with it the release of buffers, possibly the migration of calmodulin to the nucleoplasm from the cytosol, as is observed in animal systems when Ca 2+ levels become elevated (Deisseroth et al., 1998), or other changes in the nucleoplasm that free up more buffers. This result suggests that components beyond those normally associated with the Sym pathway play a vital role in shaping the Ca 2+ signature. "
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