title: BORC Functions Upstream of Kinesins 1 and 3 to Coordinate Regional Movement of Lysosomes along Different Microtubule Tracks.
abstract: The multiple functions of lysosomes are critically dependent on their ability to undergo bidirectional movement along microtubules between the center and the periphery of the cell. Centrifugal and centripetal movement of lysosomes is mediated by kinesin and dynein motors, respectively. We recently described a multi-subunit complex named BORC that recruits the small GTPase Arl8 to lysosomes to promote their kinesin-dependent movement toward the cell periphery. Here, we show that BORC and Arl8 function upstream of two structurally distinct kinesin types: kinesin-1 (KIF5B) and kinesin-3 (KIF1Bβ and KIF1A). Remarkably, KIF5B preferentially moves lysosomes on perinuclear tracks enriched in acetylated α-tubulin, whereas KIF1Bβ and KIF1A drive lysosome movement on more rectilinear, peripheral tracks enriched in tyrosinated α-tubulin. These findings establish BORC as a master regulator of lysosome positioning through coupling to different kinesins and microtubule tracks. Common regulation by BORC enables coordinate control of lysosome movement in different regions of the cell.
authors.affiliation: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Guardia
authors.affiliation: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Ginny G
authors.initials: GG
authors.lastname: Farías
authors.affiliation: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Jia
authors.affiliation: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Pu
authors.affiliation: Cell Biology and Neurobiology Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA. Electronic address: bonifacinoj@helix.nih.gov.
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
mesh_terms: D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009154:Mutation / Q000235:genetics
chemical_list: D046912:Multiprotein Complexes; D004398:Dyneins; D016547:Kinesins
keywords: Arl8; BORC; SKIP; dynein; endosomes; intracellular trafficking; kinesin; lysosomes; microtubules; tubulin modifications