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Signaling from the far side

Michela Felberbaum-Corti1, Jean Gruenberg

  • 1Department of Biochemistry, University of Geneva, 30 quai E. Ansermet, 1211, 4, Geneva, Switzerland.

Molecular Cell
|December 31, 2002
PubMed

Insights

Cell surface receptor signaling can persist intracellularly. A late endosomal p14/MP1-MAPK scaffold complex is crucial for sustained ERK pathway signaling, even after receptor downregulation.

Area of Science:

  • Cell Biology
  • Molecular Signaling
  • Endocrinology

Background:

  • Cell surface receptor signaling termination typically involves endocytosis and downregulation.
  • However, some signaling pathways exhibit sustained activity within the cell.
  • The intracellular mechanisms controlling these persistent signals are not fully understood.

Purpose of the Study:

  • To investigate the role of intracellular protein complexes in maintaining cell surface receptor signaling.
  • To identify key components involved in sustained ERK signaling from endosomes.

Main Methods:

  • Utilized advanced microscopy techniques to visualize receptor trafficking and signaling complex formation.
  • Employed biochemical assays to analyze protein-protein interactions within endosomal compartments.
  • Investigated the impact of genetic manipulation of scaffold proteins on ERK pathway activity.

Main Results:

  • Identified a p14/MP1-MAPK scaffold complex localized to late endosomes.
  • Demonstrated that this complex is essential for sustained ERK (extracellular signal-regulated kinase) pathway activation.
  • Showed that the scaffold complex facilitates signal propagation from intracellular compartments.

Conclusions:

  • A late endosomal scaffold complex involving p14/MP1 is critical for sustained ERK signaling.
  • Receptor downregulation does not necessarily abolish signaling, as intracellular scaffolds maintain pathway activity.
  • This finding reveals a novel mechanism for prolonged signal transduction within cells.

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