BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

D Splinter, DS Razafsky, Max Schlager, A Serra-Marques, I Grigoriev, Jeroen Demmers, Nanda Keijzer, Kai Jiang, I Poser, AA Hyman, CC Hoogenraad, SJ King, Anna Akhmanova

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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.
Original languageUndefined/Unknown
Pages (from-to)4226-4241
Number of pages16
JournalMolecular Biology of the Cell
Volume23
Issue number21
DOIs
Publication statusPublished - 2012

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