Abstract:
:Netrin-1 attracts or repels growing axons during development. The UNC5 receptors mediate the repulsive response, either alone or in complex with DCC receptors. The signaling mechanisms activated by UNC5 are poorly understood. Here, we examined the role of Rho GTPases in UNC5a signaling. We found that UNC5a induced neurite outgrowth in N1E-115 neuroblastoma cells in a netrin-1- and Rac1-dependent manner. UNC5a lacking its cytoplasmic tail also mediated this effect. In fibroblasts, UNC5a was able to activate RhoA and to a lower extent Rac1 and Cdc42 in response to netrin-1. Using Fluorescence Resonance Energy Transfer (FRET) intermolecular probes, we visualized the spatial and temporal activation of Rac1, Cdc42 and RhoA in live N1E-115 cells expressing UNC5a during neurite outgrowth. We found that Rac1 but not Cdc42 was transiently activated at the leading edge of the cell during neurite initiation. However, at later times when well-developed neurites were formed, active RhoA was found in the cell body and at the base of the neuronal leading process in UNC5a-expressing cells. Together, these findings demonstrate that the netrin-1 receptor UNC5a is able to induce neurite outgrowth and to differentially activate RhoA and Rac1 during neurite extension in a spatial and temporal manner.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Picard M,Petrie RJ,Antoine-Bertrand J,Saint-Cyr-Proulx E,Villemure JF,Lamarche-Vane Ndoi
10.1016/j.cellsig.2009.09.004subject
Has Abstractpub_date
2009-12-01 00:00:00pages
1961-73issue
12eissn
0898-6568issn
1873-3913pii
S0898-6568(09)00254-Xjournal_volume
21pub_type
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pub_type: 杂志文章,收录出版
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journal_title:Cellular signalling
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journal_title:Cellular signalling
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