LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning

J Cell Biol. 2017 Dec 4;216(12):4199-4215. doi: 10.1083/jcb.201703061. Epub 2017 Oct 9.


Signaling from lysosomes controls cellular clearance and energy metabolism. Lysosomal malfunction has been implicated in several pathologies, including neurodegeneration, cancer, infection, immunodeficiency, and obesity. Interestingly, many functions are dependent on the organelle position. Lysosomal motility requires the integration of extracellular and intracellular signals that converge on a competition between motor proteins that ultimately control lysosomal movement on microtubules. Here, we identify a novel upstream control mechanism of Arl8b-dependent lysosomal movement toward the periphery of the cell. We show that the C-terminal domain of lyspersin, a subunit of BLOC-1-related complex (BORC), is essential and sufficient for BORC-dependent recruitment of Arl8b to lysosomes. In addition, we establish lyspersin as the linker between BORC and late endosomal/lysosomal adaptor and mitogen activated protein kinase and mechanistic target of rapamycin activator (LAMTOR) complexes and show that epidermal growth factor stimulation decreases LAMTOR/BORC association, thereby promoting BORC- and Arl8b-dependent lysosomal centrifugal transport.

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Endosomes / drug effects
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lysosomes / drug effects
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Movement
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Transport
  • Signal Transduction


  • ARL8B protein, human
  • BLOC1S1 protein, human
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • LAMTOR1 protein, human
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Epidermal Growth Factor
  • ADP-Ribosylation Factors