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Science 3 November 2006:
Vol. 314. no. 5800, pp. 832 - 836
DOI: 10.1126/science.1134069
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Reports

The Polarity Protein Par-3 Directly Interacts with p75NTR to Regulate Myelination

Jonah R. Chan,1* Christine Jolicoeur,2 Junji Yamauchi,3 Jimmy Elliott,2 James P. Fawcett,4{ddagger} Benjamin K. Ng,1 Michel Cayouette2,5*

Cell polarity is critical in various cellular processes ranging from cell migration to asymmetric cell division and axon and dendrite specification. Similarly, myelination by Schwann cells is polarized, but the mechanisms involved remain unclear. Here, we show that the polarity protein Par-3 localizes asymmetrically in Schwann cells at the axon-glial junction and that disruption of Par-3 localization, by overexpression and knockdown, inhibits myelination. Additionally, we show that Par-3 directly associates and recruits the p75 neurotrophin receptor to the axon-glial junction, forming a complex necessary for myelination. Together, these results point to a critical role in the establishment of cell polarity for myelination.

1 Department of Cell and Neurobiology, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles 90089, USA.
2 Cellular Neurobiology Laboratory, Institut de Recherches Cliniques de Montreal (IRCM), Montreal, QC, Canada.
3 Department of Molecular Pharmacology, National Research Institute of Child Health and Development, Tokyo, Japan.
4 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
5 Département de Médecine, Université de Montréal.

{ddagger} Present address: Departments of Pharmacology and Surgery, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

* To whom correspondence should be addressed. E-mail: michel.cayouette{at}ircm.qc.ca (M.C.); jonah.chan{at}usc.edu (J.R.C.)

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Par-3-mediated Junctional Localization of the Lipid Phosphatase PTEN Is Required for Cell Polarity Establishment.
W. Feng, H. Wu, L.-N. Chan, and M. Zhang (2008)
J. Biol. Chem. 283, 23440-23449
   Abstract »    Full Text »    PDF »
Analysis of Peripheral Nerve Expression Profiles Identifies a Novel Myelin Glycoprotein, MP11.
E. J. Ryu, M. Yang, J. A. Gustin, L.-W. Chang, R. R. Freimuth, R. Nagarajan, and J. Milbrandt (2008)
J. Neurosci. 28, 7563-7573
   Abstract »    Full Text »    PDF »
ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration.
J. Yamauchi, Y. Miyamoto, J. R. Chan, and A. Tanoue (2008)
J. Cell Biol. 181, 351-365
   Abstract »    Full Text »    PDF »
Putting the glue in glia: Necls mediate Schwann cell axon adhesion.
J. R. Perlin and W. S. Talbot (2007)
J. Cell Biol. 178, 721-723
   Abstract »    Full Text »    PDF »
Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination.
P. Maurel, S. Einheber, J. Galinska, P. Thaker, I. Lam, M. B. Rubin, S. S. Scherer, Y. Murakami, D. H. Gutmann, and J. L. Salzer (2007)
J. Cell Biol. 178, 861-874
   Abstract »    Full Text »    PDF »
Myelination: all about Rac 'n' roll.
J. R. Chan (2007)
J. Cell Biol. 177, 953-955
   Abstract »    Full Text »    PDF »
Anterograde Transport and Secretion of Brain-Derived Neurotrophic Factor along Sensory Axons Promote Schwann Cell Myelination.
B. K. Ng, L. Chen, W. Mandemakers, J. M. Cosgaya, and J. R. Chan (2007)
J. Neurosci. 27, 7597-7603
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)