Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction

Cell. 2001 Apr 6;105(1):69-79. doi: 10.1016/s0092-8674(01)00297-5.

Abstract

Transmembrane B ephrins and their Eph receptors signal bidirectionally. However, neither the cell biological effects nor signal transduction mechanisms of the reverse signal are well understood. We describe a cytoplasmic protein, PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 can mediate signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein-coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. This study reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Assay
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / pharmacology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Adhesion / genetics
  • Cell Movement / drug effects
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Chemokines, CXC / pharmacology
  • Chemotactic Factors / metabolism*
  • Chemotactic Factors / pharmacology
  • Cytoplasm / metabolism
  • Ephrin-B1
  • Ephrin-B2
  • GTP-Binding Proteins*
  • GTPase-Activating Proteins*
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Protein Structure, Tertiary / physiology
  • RGS Proteins
  • Sequence Homology, Amino Acid
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Transfection
  • Two-Hybrid System Techniques
  • Xenopus

Substances

  • Brain-Derived Neurotrophic Factor
  • Carrier Proteins
  • Chemokine CXCL12
  • Chemokines, CXC
  • Chemotactic Factors
  • Cxcl12 protein, mouse
  • Ephrin-B1
  • Ephrin-B2
  • GTPase-Activating Proteins
  • Membrane Proteins
  • RGS Proteins
  • Rgs3 protein, mouse
  • GTP-Binding Proteins
  • Heterotrimeric GTP-Binding Proteins

Associated data

  • GENBANK/AF350047