An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility.
Small GTPases of the Arf and Rab families play key roles in the function of subcellular organelles. Each GTPase is usually found on only one compartment and, hence, they confer organelle specificity to many intracellular processes. However, there has so far been little evidence for specific GTPases present on lysosomes. Here, we report that two closely related human Arf-like GTPases, Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in mammalian cells, with the single homologue in Drosophila cells having a similar location. Conventionally, membrane binding of Arf and Arl proteins is mediated by both an N-terminal myristoyl group and an N-terminal amphipathic helix that is inserted into the lipid bilayer upon activation of the GTPase. Arl8a and Arl8b do not have N-terminal myristoylation sites, and we find that Arl8b is instead N-terminally acetylated, and an acetylated methionine is necessary for its lysosomal localization. Overexpression of Arl8a or Arl8b results in a microtubule-dependent redistribution of lysosomes towards the cell periphery. Live cell imaging shows that lysosomes move more frequently both toward and away from the cell periphery, suggesting a role for Arl8a and Arl8b as positive regulators of lysosomal transport.
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK.
Irmgard
I
Hofmann
Sean
S
Munro
D020727:ADP-Ribosylation Factors / Q000235:genetics* / Q000378:metabolism*; D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002522:Chlorocebus aethiops; D019143:Evolution, Molecular; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C511801:ARL8B protein, human; C114750:TCF20 protein, human; D014157:Transcription Factors; C512609:ARL8A protein, human; D020558:GTP Phosphohydrolases; D020727:ADP-Ribosylation Factors