Linked Life Data

21471251

Source:http://linkedlifedata.com/resource/pubmed/id/21471251

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-7-1
pubmed:abstractText
ERK1/2 is required for certain forms of synaptic plasticity, including the long-term potentiation of synaptic strength. However, the molecular mechanisms regulating synaptically localized ERK1/2 signaling are poorly understood. Here, we show that the MAPK scaffold protein kinase suppressor of Ras 1 (KSR1) is directly phosphorylated by the downstream kinase ERK1/2. Quantitative Western blot analysis further demonstrates that expression of mutated, feedback-deficient KSR1 promotes sustained ERK1/2 activation in HEK293 cells in response to EGF stimulation, compared to a more transient activation in control cells expressing wild-type KSR1. Immunocytochemistry and confocal imaging of primary hippocampal neurons from newborn C57BL6 mice further show that feedback phosphorylation of KSR1 significantly reduces its localization to dendritic spines. This effect can be reversed by tetrodotoxin (1 ?M) or PD184352 (2 ?M) treatment, further suggesting that neuronal activity and phosphorylation by ERK1/2 lead to KSR1 removal from the postsynaptic compartment. Consequently, electrophysiological recordings in hippocampal neurons expressing wild-type or feedback-deficient KSR1 demonstrate that KSR1 feedback phosphorylation restricts the potentiation of excitatory postsynaptic currents. Our findings, therefore, suggest that feedback phosphorylation of the scaffold protein KSR1 prevents excessive ERK1/2 signaling in the postsynaptic compartment and thus contributes to maintaining physiological levels of synaptic excitability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2362-72
pubmed:meshHeading
pubmed-meshheading:21471251-Amino Acid Sequence, pubmed-meshheading:21471251-Animals, pubmed-meshheading:21471251-Benzamides, pubmed-meshheading:21471251-Binding Sites, pubmed-meshheading:21471251-Blotting, Western, pubmed-meshheading:21471251-Cells, Cultured, pubmed-meshheading:21471251-Dendritic Spines, pubmed-meshheading:21471251-Excitatory Postsynaptic Potentials, pubmed-meshheading:21471251-Feedback, Physiological, pubmed-meshheading:21471251-HEK293 Cells, pubmed-meshheading:21471251-Hippocampus, pubmed-meshheading:21471251-Humans, pubmed-meshheading:21471251-Male, pubmed-meshheading:21471251-Mice, pubmed-meshheading:21471251-Mice, Inbred C57BL, pubmed-meshheading:21471251-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:21471251-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:21471251-Molecular Sequence Data, pubmed-meshheading:21471251-Mutation, pubmed-meshheading:21471251-Neuronal Plasticity, pubmed-meshheading:21471251-Neurons, pubmed-meshheading:21471251-Phosphorylation, pubmed-meshheading:21471251-Protein Kinases, pubmed-meshheading:21471251-Sequence Homology, Amino Acid, pubmed-meshheading:21471251-Synapses
pubmed:year
2011
pubmed:articleTitle
Compartmentalization of the MAPK scaffold protein KSR1 modulates synaptic plasticity in hippocampal neurons.
pubmed:affiliation
Warwick Medical School, University of Warwick, Gibbet Hill Rd., Coventry CV4 7AL, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't