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

Author:

Splinter Daniël1,Razafsky David S.2,Schlager Max A.3,Serra-Marques Andrea4,Grigoriev Ilya14,Demmers Jeroen5,Keijzer Nanda3,Jiang Kai4,Poser Ina6,Hyman Anthony A.6,Hoogenraad Casper C.34,King Stephen J.2,Akhmanova Anna14

Affiliation:

1. Department of Cell Biology, Erasmus Medical Centre, 3000 CA Rotterdam, Netherlands

2. Division of Molecular Biology and Biochemistry, University of Missouri–Kansas City, Kansas City, MO 64110

3. Department of Neuroscience, Erasmus Medical Centre, 3000 CA Rotterdam, Netherlands

4. Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands

5. Proteomics Centre, Erasmus Medical Centre, 3000 CA Rotterdam, Netherlands

6. Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany

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.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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