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Published online June 16, 2008
doi:10.1083/jcb.200803150
The Journal of Cell Biology, Vol. 181, No. 6, 1027-1039
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Ha et al.
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Article

A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes



Junghoon Ha1, Kevin W.-H. Lo1, Kenneth R. Myers1, Tiffany M. Carr1, Michael K. Humsi1, Bareza A. Rasoul1, Rosalind A. Segal2,3, and K. Kevin Pfister1

1 Department of Cell Biology, School of Medicine, University of Virginia, Charlottesville, VA 22908
2 Department of Neurobiology and 3 Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Harvard University, Boston, MA 02115

Correspondence to K. Kevin Pfister: kkp9w{at}virginia.edu

Cytoplasmic dynein is the multisubunit motor protein for retrograde movement of diverse cargoes to microtubule minus ends. Here, we investigate the function of dynein variants, defined by different intermediate chain (IC) isoforms, by expressing fluorescent ICs in neuronal cells. Green fluorescent protein (GFP)–IC incorporates into functional dynein complexes that copurify with membranous organelles. In living PC12 cell neurites, GFP–dynein puncta travel in both the anterograde and retrograde directions. In cultured hippocampal neurons, neurotrophin receptor tyrosine kinase B (TrkB) signaling endosomes are transported by cytoplasmic dynein containing the neuron-specific IC-1B isoform and not by dynein containing the ubiquitous IC-2C isoform. Similarly, organelles containing TrkB isolated from brain by immunoaffinity purification also contain dynein with IC-1 but not IC-2 isoforms. These data demonstrate that the IC isoforms define dynein populations that are selectively recruited to transport distinct cargoes.

J. Ha and K.W.-H. Lo contributed equally to this paper.

Abbreviations used in this paper: IC, intermediate chain; mRFP, monomeric red fluorescent protein; Trk, neurotrophin tyrosine receptor kinase.

© 2008 Ha et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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