Bicaudal D is an evolutionarily conserved protein, which is involved in dynein-mediated motility both in Drosophila and in mammals. Here we report that the N-terminal portion of human Bicaudal D2 (BICD2) is capable of inducing microtubule minus end-directed movement independently of the molecular context. This characteristic offers a new tool to exploit the relocalization of different cellular components by using appropriate targeting motifs. Here, we use the BICD2 N-terminal domain as a chimera with mitochondria and peroxisome-anchoring sequences to demonstrate the rapid dynein-mediated transport of selected organelles. Surprisingly, unlike other cytoplasmic dynein-mediated processes, this transport shows very low sensitivity to overexpression of the dynactin subunit dynamitin. The dynein-recruiting activity of the BICD2 N-terminal domain is reduced within the full-length molecule, indicating that the C-terminal part of the protein might regulate the interaction between BICD2 and the motor complex. Our findings provide a novel model system for dissection of the molecular mechanism of dynein motility.

Drosophila Proteins/genetics/*metabolism, Dynein ATPase/*metabolism, Genes, Reporter, Humans, Lipoproteins/genetics/metabolism, Membrane Proteins/genetics/metabolism, Microtubule-Associated Proteins/metabolism, Microtubule-Organizing Center/metabolism, Microtubules/*metabolism, Mitochondria/metabolism, Peroxisomes/metabolism, Recombinant Fusion Proteins/genetics/metabolism, Research Support, Non-U.S. Gov't,
EMBO Journal
Erasmus MC: University Medical Center Rotterdam

Hoogenraad, C.C, Wulf, P, Schiefermeier, N, Stepanova, T, Galjart, N.J, Small, J.V, … Akhmanova, A.S. (2003). Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO Journal, 22(22), 6004–6015. doi:10.1093/emboj/cdg592