p18/LAMTOR1: a late endosome/lysosome-specific anchor protein for the mTORC1/MAPK signaling pathway

Methods Enzymol. 2014;535:249-63. doi: 10.1016/B978-0-12-397925-4.00015-8.

Abstract

p18/LAMTOR1 is a membrane protein specifically localized to the surface of late endosomes/lysosomes that serves as an anchor for the "Ragulator" complex, which contains p14/LAMTOR2, MP1/LAMTOR3, HBXIP, and C7orf59. The Ragulator interacts with RagAB/CD GTPases and V-ATPase and plays crucial roles for activation of mammalian target of rapamycin complex 1 (mTORC1) on the lysosomal surface. Activated mTORC1 orchestrates various cellular functions, for example, macromolecule biosynthesis, energy metabolism, autophagy, cell growth, responses to growth factors, and the trafficking and maturation of lysosomes. The Ragulator can also regulate a branch of the MAPK pathway by recruiting MEK1 to MP1/LAMTOR3. These findings suggest that p18/LAMTOR1 creates a core platform for intracellular signaling pathways that function via late endosomes/lysosomes.

Keywords: Late endosome; MAPK; lysosome; mTOR; membrane microdomain; p18. LAMTOR1. Ragulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Fractionation
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins / biosynthesis
  • Lysosomes / metabolism
  • MAP Kinase Signaling System*
  • Mechanistic Target of Rapamycin Complex 1
  • Membrane Microdomains
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Multiprotein Complexes / metabolism*
  • PC12 Cells
  • Protein Interaction Mapping
  • Protein Transport
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LAMTOR1 protein, human
  • Luminescent Proteins
  • Multiprotein Complexes
  • Recombinant Fusion Proteins
  • lipid raft adaptor p18 protein, mouse
  • red fluorescent protein
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases