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Originally published as MBC in Press, 10.1091/mbc.E03-06-0376 on October 31, 2003

Vol. 14, Issue 12, 5069-5081, December 2003

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A Role for Intermediate Filaments in Determining and Maintaining the Shape of Nerve Cells

Brian T. Helfand *, Melissa G. Mendez *, Jason Pugh *, Claude Delsert {dagger}, and Robert D. Goldman * {ddagger}

* Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611; {ddagger} Institut Français de Recherche pour l'Exploitation de la Mer, Centre de Recherche en Biochimie des Macromolécules-Centre National de la Recherche Scientifique, 1919, 34293 Montpellier, France

Submitted June 9, 2003; Revised July 23, 2003; Accepted July 28, 2003
Monitoring Editor: Lawrence Goldstein

To date, the functions of most neural intermediate filament (IF) proteins have remained elusive. Peripherin is a type III intermediate filament (IF) protein that is expressed in developing and in differentiated neurons of the peripheral and enteric nervous systems. It is also the major IF protein expressed in PC12 cells, a widely used model for studies of peripheral neurons. Dramatic increases in peripherin expression have been shown to coincide with the initiation and outgrowth of axons during development and regeneration, suggesting that peripherin plays an important role in axon formation. Recently, small interfering RNAs (siRNA) have provided efficient ways to deplete specific proteins within mammalian cells. In this study, it has been found that peripherin-siRNA depletes peripherin and inhibits the initiation, extension, and maintenance of neurites in PC12 cells. Furthermore, the results of these experiments demonstrate that peripherin IF are critical determinants of the overall shape and architecture of neurons.


Abbreviations used: CM, complete medium; DM, differentiation medium; IF, intermediate filament(s); MT, microtubules; NF, neurofilament(s); siRNA, small interfering ribonucleic acid.

The online version of this article contains supplementary video material. The online version is available at www.molbiolcell.org.

{ddagger} Corresponding author. E-mail address: r-goldman{at}northwestern.edu.




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