The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes

EMBO J. 2009 Mar 4;28(5):477-89. doi: 10.1038/emboj.2008.308. Epub 2009 Jan 29.

Abstract

The regulation of endosome dynamics is crucial for fundamental cellular functions, such as nutrient intake/digestion, membrane protein cycling, cell migration and intracellular signalling. Here, we show that a novel lipid raft adaptor protein, p18, is involved in controlling endosome dynamics by anchoring the MEK1-ERK pathway to late endosomes. p18 is anchored to lipid rafts of late endosomes through its N-terminal unique region. p18(-/-) mice are embryonic lethal and have severe defects in endosome/lysosome organization and membrane protein transport in the visceral endoderm. p18(-/-) cells exhibit apparent defects in endosome dynamics through perinuclear compartment, such as aberrant distribution and/or processing of lysosomes and impaired cycling of Rab11-positive recycling endosomes. p18 specifically binds to the p14-MP1 complex, a scaffold for MEK1. Loss of p18 function excludes the p14-MP1 complex from late endosomes, resulting in a downregulation of the MEK-ERK activity. These results indicate that the lipid raft adaptor p18 is essential for anchoring the MEK-ERK pathway to late endosomes, and shed new light on a role of endosomal MEK-ERK pathway in controlling endosome dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Signal Transducing / physiology*
  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Endocytosis / drug effects
  • Endocytosis / physiology
  • Endoderm / embryology
  • Endoderm / metabolism
  • Endosomes / metabolism*
  • Epidermal Growth Factor / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / physiology*
  • Lysosomes / metabolism
  • MAP Kinase Kinase 1 / metabolism*
  • Membrane Microdomains / metabolism*
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Protein Binding
  • Proteins / metabolism
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • LAMTOR2 protein, mouse
  • Lamtor3 protein, mouse
  • Proteins
  • lipid raft adaptor p18 protein, mouse
  • lipid raft adaptor p18 protein, rat
  • Epidermal Growth Factor
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase 1