EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains

Neuron. 1999 Mar;22(3):511-24. doi: 10.1016/s0896-6273(00)80706-0.

Abstract

Transmembrane ephrinB proteins have important functions during embryonic patterning as ligands for Eph receptor tyrosine kinases and presumably as signal-transducing receptor-like molecules. Consistent with "reverse" signaling, ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains, platforms for the localized concentration and activation of signaling molecules. Glutamate receptor-interacting protein (GRIP) and a highly related protein, which we have termed GRIP2, are recruited into these rafts through association with the C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble EphB2 receptor ectodomain causes the formation of large raft patches that also contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Brain / embryology
  • Brain / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Ephrin-B1
  • Gene Deletion
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Organ Specificity
  • Phosphoamino Acids / metabolism
  • Precipitin Tests
  • Protein-Serine-Threonine Kinases / metabolism
  • Rats

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Ephrin-B1
  • Grip1 protein, mouse
  • Grip1 protein, rat
  • Grip2 protein, mouse
  • Grip2 protein, rat
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphoamino Acids
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/AF072509
  • GENBANK/AJ133439