Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport

EMBO J. 2003 Nov 17;22(22):6004-15. doi: 10.1093/emboj/cdg592.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Dynactin Complex
  • Dyneins / metabolism*
  • Genes, Reporter
  • Humans
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Organizing Center / metabolism
  • Microtubules / metabolism*
  • Mitochondria / metabolism
  • Peroxins
  • Peroxisomes / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism

Substances

  • BicD protein, Drosophila
  • DCTN2 protein, human
  • Drosophila Proteins
  • Dynactin Complex
  • Lipoproteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Peroxins
  • Pex3 protein, human
  • Recombinant Fusion Proteins
  • Dyneins