title: BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures.
abstract: Cytoplasmic dynein is the major microtubule minus-end-directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein-dynactin interaction are poorly understood. In this study, we focus on dynein-dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N-dynein-dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end-directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors.
authors.affiliation: Department of Cell Biology, Erasmus Medical Centre, 3000 CA Rotterdam, Netherlands Department of Neuroscience, Erasmus Medical Centre, 3000 CA Rotterdam, The Netherlands.
authors.forename: Daniël
authors.initials: D
authors.lastname: Splinter
authors.forename: David S
authors.initials: DS
authors.lastname: Razafsky
authors.forename: Max A
authors.initials: MA
authors.lastname: Schlager
authors.forename: Andrea
authors.initials: A
authors.lastname: Serra-Marques
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Nanda
authors.initials: N
authors.lastname: Keijzer
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Hyman
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: King
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D021381:Protein Transport; D022161:Transport Vesicles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism
chemical_list: C435206:Bicd2 protein, mouse; D002352:Carrier Proteins; D000072159:Dynactin Complex; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins; D020691:rab GTP-Binding Proteins