Kinase Suppressor of Ras1 Compartmentalizes Hippocampal Signal Transduction and Subserves Synaptic Plasticity and Memory Formation

Sara C. Shalin, Caterina M. Hernandez, Michele K. Dougherty, Deborah K. Morrison, J. David Sweatt

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

The ERK/MAP kinase cascade is important for long-term memory formation and synaptic plasticity, with a myriad of upstream signals converging upon ERK activation. Despite this convergence of signaling, neurons routinely activate appropriate biological responses to different stimuli. Scaffolding proteins represent a mechanism to achieve compartmentalization of signaling and the appropriate targeting of ERK-dependent processes. We report that kinase suppressor of Ras (KSR1) functions biochemically in the hippocampus to scaffold the components of the ERK cascade, specifically regulating the cascade when a membrane fraction of ERK is activated via a PKC-dependent pathway but not via a cAMP/PKA-dependent pathway. Specificity of KSR1-dependent signaling also extends to specific downstream targets of ERK. Behaviorally and physiologically, we found that the absence of KSR1 leads to deficits in associative learning and theta burst stimulation-induced LTP. Our report provides novel insight into the endogenous scaffolding role of KSR1 in controlling kinase activation within the nervous system.

Original languageEnglish (US)
Pages (from-to)765-779
Number of pages15
JournalNeuron
Volume50
Issue number5
DOIs
StatePublished - Jun 1 2006

Keywords

  • MOLNEURO
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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