Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 6 December 2011
Vol. 4, Issue 202, p. ra82
[DOI: 10.1126/scisignal.2002060]


Editor's Summary

Promoting Neurite Retraction with ProNGF
Nerve growth factor (NGF), which was identified because of its ability to stimulate neurite outgrowth, promotes neuronal survival and differentiation during development. Like other neurotrophins, NGF is synthesized through cleavage of a precursor form and, here, Deinhardt et al. show that this precursor form (proNGF) induced the acute collapse and retraction of growth cones in cultured hippocampal neurons. ProNGF bound to a complex of the p75 neurotrophin receptor (p75NTR, which also acts as a co-receptor for NGF and other neurotrophins) and SorCS2 to stimulate neurite collapse through two distinct mechanisms. It promoted dissociation of the guanine nucleotide exchange factor Trio from the p75NTR-SorCS2 complex, decreasing activity of the Rac guanosine triphosphatase, and, in parallel, stimulated the phosphorylation and inactivation of the actin-bundling protein fascin. Thus, whereas NGF promotes neurite outgrowth, proNGF signals through a distinct pathway to elicit neurite retraction.

Citation: K. Deinhardt, T. Kim, D. S. Spellman, R. E. Mains, B. A. Eipper, T. A. Neubert, M. V. Chao, B. L. Hempstead, Neuronal Growth Cone Retraction Relies on Proneurotrophin Receptor Signaling Through Rac. Sci. Signal. 4, ra82 (2011).

Read the Full Text

MiR-592 Regulates the Induction and Cell Death-Promoting Activity of p75NTR in Neuronal Ischemic Injury.
K. Irmady, K. A. Jackman, V. A. Padow, N. Shahani, L. A. Martin, L. Cerchietti, K. Unsicker, C. Iadecola, and B. L. Hempstead (2014)
J. Neurosci. 34, 3419-3428
   Abstract »    Full Text »    PDF »
Antipsychotics Activate mTORC1-Dependent Translation to Enhance Neuronal Morphological Complexity.
H. Bowling, G. Zhang, A. Bhattacharya, L. M. Perez-Cuesta, K. Deinhardt, C. A. Hoeffer, T. A. Neubert, W.-b. Gan, E. Klann, and M. V. Chao (2014)
Science Signaling 7, ra4
   Abstract »    Full Text »    PDF »
Fascin Regulates the Migration of Subventricular Zone-Derived Neuroblasts in the Postnatal Brain.
M. Sonego, S. Gajendra, M. Parsons, Y. Ma, C. Hobbs, M. P. Zentar, G. Williams, L. M. Machesky, P. Doherty, and G. Lalli (2013)
J. Neurosci. 33, 12171-12185
   Abstract »    Full Text »    PDF »
ProNGF promotes neurite growth from a subset of NGF-dependent neurons by a p75NTR-dependent mechanism.
L. Howard, S. Wyatt, G. Nagappan, and A. M. Davies (2013)
Development 140, 2108-2117
   Abstract »    Full Text »    PDF »
Of Proneurotrophins and Their Antineurotrophic Effects.
L. Kotlyanskaya, K. A. McLinden, and E. Giniger (2013)
Science Signaling 6, pe6
   Abstract »    Full Text »    PDF »
A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions.
R. Kraft, A. Kahn, J. L. Medina-Franco, M. L. Orlowski, C. Baynes, F. Lopez-Vallejo, K. Barnard, G. M. Maggiora, and L. L. Restifo (2013)
Dis. Model. Mech. 6, 217-235
   Abstract »    Full Text »    PDF »
The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.
J. E. Pick, M. Malumbres, and E. Klann (2012)
Learn. Mem. 20, 11-20
   Abstract »    Full Text »    PDF »
ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation.
C.-J. Siao, C. U. Lorentz, P. Kermani, T. Marinic, J. Carter, K. McGrath, V. A. Padow, W. Mark, D. J. Falcone, L. Cohen-Gould, et al. (2012)
J. Exp. Med. 209, 2291-2305
   Abstract »    Full Text »    PDF »
Vps10 Family Proteins and the Retromer Complex in Aging-Related Neurodegeneration and Diabetes.
R. F. Lane, P. St George-Hyslop, B. L. Hempstead, S. A. Small, S. M. Strittmatter, and S. Gandy (2012)
J. Neurosci. 32, 14080-14086
   Abstract »    Full Text »    PDF »
Dependence of Regenerated Sensory Axons on Continuous Neurotrophin-3 Delivery.
S. Hou, L. Nicholson, E. van Niekerk, M. Motsch, and A. Blesch (2012)
J. Neurosci. 32, 13206-13220
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882