QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 11, 5092-5100, November 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E04-05-0401v1 15/11/5092    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wagner, O. I. Articles by Holzbaur, E. L. F. Search for Related Content PubMed PubMed Citation Articles by Wagner, O. I. Articles by Holzbaur, E. L. F.

The Interaction of Neurofilaments with the Microtubule Motor Cytoplasmic Dynein

Oliver I. Wagner ^* , Jennifer Ascaño , Mariko Tokito , Jean-Francois Leterrier , Paul A. Janmey ^* , and Erika L. F. Holzbaur  

^* Institute of Medicine and Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085; Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085; and UMR Centré Nacional pour la Recherche Scientifique 6558, University of Poitiers, 86022 Poitiers, France

Submitted May 14, 2004; Revised August 4, 2004; Accepted August 16, 2004
Monitoring Editor: J. Richard McIntosh

Neurofilaments are synthesized in the cell body of neurons and transported outward along the axon via slow axonal transport. Direct observation of neurofilaments trafficking in live cells suggests that the slow outward rate of transport is due to the net effects of anterograde and retrograde microtubule motors pulling in opposition. Previous studies have suggested that cytoplasmic dynein is required for efficient neurofilament transport. In this study, we examine the interaction of neurofilaments with cytoplasmic dynein. We used fluid tapping mode atomic force microscopy to visualize single neurofilaments, microtubules, dynein/dynactin, and physical interactions between these neuronal components. AFM images suggest that neurofilaments act as cargo for dynein, associating with the base of the motor complex. Yeast two-hybrid and affinity chromatography assays confirm this hypothesis, indicating that neurofilament subunit M binds directly to dynein IC. This interaction is blocked by monoclonal antibodies directed either to NF-M or to dynein. Together these data suggest that a specific interaction between neurofilament subunit M and cytoplasmic dynein is involved in the saltatory bidirectional motility of neurofilaments undergoing axonal transport in the neuron.

Corresponding author. E-mail address: holzbaur{at}mail.med.upenn.edu.

This article has been cited by other articles:

				J. P. Caviston, J. L. Ross, S. M. Antony, M. Tokito, and E. L. F. Holzbaur Huntingtin facilitates dynein/dynactin-mediated vesicle transport PNAS, June 12, 2007; 104(24): 10045 - 10050. [Abstract] [Full Text] [PDF]

				N. Trivedi, P. Jung, and A. Brown Neurofilaments Switch between Distinct Mobile and Stationary States during Their Transport along Axons J. Neurosci., January 17, 2007; 27(3): 507 - 516. [Abstract] [Full Text] [PDF]

				K. W.-H. Lo, H.-M. Kan, and K. K. Pfister Identification of a Novel Region of the Cytoplasmic Dynein Intermediate Chain Important for Dimerization in the Absence of the Light Chains J. Biol. Chem., April 7, 2006; 281(14): 9552 - 9559. [Abstract] [Full Text] [PDF]

				A. Brown, L. Wang, and P. Jung Stochastic Simulation of Neurofilament Transport in Axons: The "Stop-and-Go" Hypothesis Mol. Biol. Cell, September 1, 2005; 16(9): 4243 - 4255. [Abstract] [Full Text] [PDF]

				Y. He, F. Francis, K. A. Myers, W. Yu, M. M. Black, and P. W. Baas Role of cytoplasmic dynein in the axonal transport of microtubules and neurofilaments J. Cell Biol., February 28, 2005; 168(5): 697 - 703. [Abstract] [Full Text] [PDF]