Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/134115
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA |
Author: | Sun, Y. Lim, Y. Li, F. Liu, S. Lu, J.J. Haberberger, R. Zhong, J.H. Zhou, X.F. |
Citation: | PLoS One, 2012; 7(4):1-12 |
Publisher: | Public Library Science |
Issue Date: | 2012 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Obukhov, A.G. |
Statement of Responsibility: | Ying Sun, Yoon Lim, Fang Li, Shen Liu, Jian-Jun Lu, Rainer Haberberger ... et al. |
Abstract: | Background Neurons extend their dendrites and axons to build functional neural circuits, which are regulated by both positive and negative signals during development. Brain-derived neurotrophic factor (BDNF) is a positive regulator for neurite outgrowth and neuronal survival but the functions of its precursor (proBDNF) are less characterized. Methodology/principal findings Here we show that proBDNF collapses neurite outgrowth in murine dorsal root ganglion (DRG) neurons and cortical neurons by activating RhoA via the p75 neurotrophin receptor (p75NTR). We demonstrated that the receptor proteins for proBDNF, p75NTR and sortilin, were highly expressed in cultured DRG or cortical neurons. ProBDNF caused a dramatic neurite collapse in a dose-dependent manner and this effect was about 500 fold more potent than myelin-associated glycoprotein. Neutralization of endogenous proBDNF by using antibodies enhanced neurite outgrowth in vitro and in vivo, but this effect was lost in p75NTR(-/-) mice. The neurite outgrowth of cortical neurons from p75NTR deficient (p75NTR(-/-)) mice was insensitive to proBDNF. There was a time-dependent reduction of length and number of filopodia in response to proBDNF which was accompanied with a polarized RhoA activation in growth cones. Moreover, proBDNF treatment of cortical neurons resulted in a time-dependent activation of RhoA but not Cdc42 and the effect was absent in p75NTR(-/-) neurons. Rho kinase (ROCK) and the collapsin response mediator protein-2 (CRMP-2) were also involved in the proBDNF action. Conclusions proBDNF has an opposing role in neurite outgrowth to that of mature BDNF. Our observations suggest that proBDNF collapses neurites outgrowth and filopodial growth cones by activating RhoA through the p75NTR signaling pathway. |
Keywords: | Ganglia, Spinal Neurites Nerve Fibers Cells, Cultured Pseudopodia Animals Mice, Knockout Mice rho GTP-Binding Proteins Brain-Derived Neurotrophic Factor Receptors, Nerve Growth Factor Adaptor Proteins, Vesicular Transport Protein Precursors Antibodies Signal Transduction Gene Expression Regulation, Developmental Time-Lapse Imaging |
Rights: | © 2012 Sun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0035883 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/595937 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0035883 |
Appears in Collections: | Medical Sciences publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_134115.pdf | Published version | 2.75 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.