Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport.
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.
Hoogenraad
Casper C
CC
MGC Department of Neuroscience, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Wulf
Phebe
P
Schiefermeier
Natalia
N
Stepanova
Tatiana
T
Galjart
Niels
N
Small
J Victor
JV
Grosveld
Frank
F
de Zeeuw
Chris I
CI
Akhmanova
Anna
A
D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D000074401:Peroxins; D020675:Peroxisomes / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
C061998:BicD protein, Drosophila; C000606361:DCTN2 protein, human; D029721:Drosophila Proteins; D000072159:Dynactin Complex; D008074:Lipoproteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000074401:Peroxins; C113138:Pex3 protein, human; D011993:Recombinant Fusion Proteins; D004398:Dyneins