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A dual role for the adaptor protein DRK in Drosophila olfactory learning and memory

Academic Article
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Overview

authors

  • Moressis, A.
  • Friedrich, A. R.
  • Pavlopoulos, E.
  • Davis, Ronald
  • Skoulakis, E. M. C.

publication date

  • February 2009

journal

  • Journal of Neuroscience  Journal

abstract

  • Participation of RAS, RAF, and mitogen-activated protein kinase (MAPK) in learning and memory has been demonstrated in a number of studies, but the molecular events requisite for cascade activation and regulation have not been explored. We demonstrate that the adapter protein DRK (downstream of receptor kinase) which is essential for signaling to RAS in developmental contexts, is preferentially distributed in the adult mushroom bodies, centers for olfactory learning and memory. We demonstrate that drk mutant heterozygotes exhibit deficits in olfactory learning and memory, apparent under limited training conditions, but are not impaired in sensory responses requisite for the association of the stimuli, or brain neuroanatomy. Furthermore, we demonstrate that the protein is required acutely within mushroom body neurons to mediate efficient learning, a process that requires RAF activation. Importantly, 90 min memory remained impaired, even after differential training yielding equivalent learning in animals with compromised DRK levels and controls and did not require RAF. Sustained MAPK activation is compromised in drk mutants and surprisingly is negatively regulated by constitutive RAF activity. The data establish a role for DRK in Drosophila behavioral neuroplasticity and suggest a dual role for the protein, first in RAF activation-dependent learning and additionally in RAF-inhibition dependent sustained MAPK activation essential for memory formation or stability.

subject areas

  • Analysis of Variance
  • Animals
  • Animals, Genetically Modified
  • Association Learning
  • Conditioning, Classical
  • Drosophila
  • Drosophila Proteins
  • Glue Proteins, Drosophila
  • Learning Disorders
  • Memory Disorders
  • Memory, Short-Term
  • Mitogen-Activated Protein Kinase Kinases
  • Mushroom Bodies
  • Mutation
  • Odorants
  • Olfactory Pathways
  • RNA, Small Interfering
  • Smell
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Research

keywords

  • DRK
  • RAF
  • RAS
  • learning
  • memory
  • signaling
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Identity

PubMed Central ID

  • PMC2693346

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.3670-08.2009

PubMed ID

  • 19244537
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Additional Document Info

start page

  • 2611

end page

  • 2625

volume

  • 29

issue

  • 8

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