Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway - PubMed (original) (raw)
. 2001 Oct 12;294(5541):333-9.
doi: 10.1126/science.1063395.
Affiliations
- PMID: 11598293
- DOI: 10.1126/science.1063395
Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway
R E Dolmetsch et al. Science. 2001.
Abstract
Increases in the intracellular concentration of calcium ([Ca2+]i) activate various signaling pathways that lead to the expression of genes that are essential for dendritic development, neuronal survival, and synaptic plasticity. The mode of Ca2+ entry into a neuron plays a key role in determining which signaling pathways are activated and thus specifies the cellular response to Ca2+. Ca2+ influx through L-type voltage-activated channels (LTCs) is particularly effective at activating transcription factors such as CREB and MEF-2. We developed a functional knock-in technique to investigate the features of LTCs that specifically couple them to the signaling pathways that regulate gene expression. We found that an isoleucine-glutamine ("IQ") motif in the carboxyl terminus of the LTC that binds Ca2+-calmodulin (CaM) is critical for conveying the Ca2+ signal to the nucleus. Ca2+-CaM binding to the LTC was necessary for activation of the Ras/mitogen-activated protein kinase (MAPK) pathway, which conveys local Ca2+ signals from the mouth of the LTC to the nucleus. CaM functions as a local Ca2+ sensor at the mouth of the LTC that activates the MAPK pathway and leads to the stimulation of genes that are essential for neuronal survival and plasticity.
Comment in
- Signal transduction. Calcium channels--link locally, act globally.
Ikeda SR. Ikeda SR. Science. 2001 Oct 12;294(5541):318-9. doi: 10.1126/science.1066160. Science. 2001. PMID: 11598289 No abstract available.
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