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Retrograde neurotrophic signaling requires a protein interacting with receptor tyrosine kinases via C2H2 zinc fingers

Academic Article
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Overview

authors

  • Fu, X.
  • Zang, K.
  • Zhou, Z.
  • Reichardt, L. F.
  • Xu, Baoji

publication date

  • January 2010

journal

  • Molecular Biology of the Cell  Journal

abstract

  • Neurotrophins at axonal terminals signal to cell bodies to regulate neuronal development via signaling endosomes containing activated Trk receptor tyrosine kinases and mitogen-activated protein kinases (MAPKs). Requirements for the formation of signaling endosomes remain, however, poorly characterized. Here we show that a novel Trk-interacting protein, NTRAP (neurotrophic factor receptor-associated protein), plays a crucial role in this signaling process. NTRAP interacts with the Trk intracellular domain through its C(2)H(2) zinc fingers in a kinase-dependent manner. It is associated with vesicles, some of which contain markers for signaling endosomes. Inhibition of NTRAP function suppresses neurotrophin-induced neurite outgrowth in PC12 cells by altering TrkA endocytic traffic, inhibiting the formation of endosomes containing persistently active MAPKs. In compartmentalized sensory neuron cultures, down-regulation of NTRAP abolishes the ability of neurotrophins applied to distal axons to activate the transcription factor adenosine 3',5'-monophosphate response element-binding protein (CREB) and to promote neuronal survival. We propose that NTRAP regulates retrograde neurotrophic signaling by controlling the formation of signaling endosomes.

subject areas

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • Cell Differentiation
  • Endocytosis
  • Endosomes
  • Enzyme Activation
  • Mice
  • Mitogen-Activated Protein Kinases
  • Molecular Sequence Data
  • Nerve Growth Factors
  • PC12 Cells
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • Protein Transport
  • Rats
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Sensory Receptor Cells
  • Signal Transduction
  • Zinc Fingers
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Identity

PubMed Central ID

  • PMC2801717

International Standard Serial Number (ISSN)

  • 1059-1524

Digital Object Identifier (DOI)

  • 10.1091/mbc.E09-04-0321

PubMed ID

  • 19864463
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Additional Document Info

start page

  • 36

end page

  • 49

volume

  • 21

issue

  • 1

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