BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures
Molecular Biology of the Cell (Print) , Volume 23 - Issue 21 p. 4226- 4241
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.
|Molecular Biology of the Cell (Print)|
|Organisation||Department of Neuroscience|
Splinter, D, Razafsky, D.S, Schlager, M.A, Serra-Marques, A, Grigoriev, I, Demmers, J.A.A, … Akhmanova, A.S. (2012). BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures. Molecular Biology of the Cell (Print), 23(21), 4226–4241. doi:10.1091/mbc.E12-03-0210