The calcium‐activated protease calpain regulates netrin‐1 receptor deleted in colorectal cancer‐induced axon outgrowth in cortical neurons

2019 ◽  
Vol 152 (3) ◽  
pp. 315-332 ◽  
Author(s):  
Philippe M. Duquette ◽  
Nathalie Lamarche‐Vane
Keyword(s):  
Colorectal Cancer ◽  
Cortical Neurons ◽  
Axon Outgrowth ◽  
Deleted In Colorectal Cancer

Netrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation

Nature ◽  
2002 ◽  
Vol 417 (6887) ◽  
pp. 443-447 ◽  
Author(s):  
Christelle Forcet ◽  
Elke Stein ◽  
Laurent Pays ◽  
Véronique Corset ◽  
Fabien Llambi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Axon Outgrowth ◽  
Mapk Activation ◽  
Deleted In Colorectal Cancer

scholarly journals Trio Mediates Netrin-1-Induced Rac1 Activation in Axon Outgrowth and Guidance

2008 ◽  
Vol 28 (7) ◽  
pp. 2314-2323 ◽  
Author(s):  
Anne Briançon-Marjollet ◽  
Atefeh Ghogha ◽  
Homaira Nawabi ◽  
Ibtissem Triki ◽  
Camille Auziol ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Anterior Commissure ◽  
Internal Capsule ◽  
Axon Outgrowth ◽  
Nucleotide Exchange ◽  
Deleted In Colorectal Cancer ◽  
Commissural Axons ◽  
Guidance Cue ◽  
Axonal Projections ◽  
Nucleotide Exchange Factor

ABSTRACT The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. The guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 activation has not yet been identified. Here, we show that the RhoGEF Trio mediates Rac1 activation in netrin-1 signaling. We found that Trio interacts with the netrin-1 receptor DCC in mouse embryonic brains and that netrin-1-induced Rac1 activation in brain is impaired in the absence of Trio. Trio−/− cortical neurons fail to extend neurites in response to netrin-1, while they are able to respond to glutamate. Accordingly, netrin-1-induced commissural axon outgrowth is reduced in Trio−/− spinal cord explants, and the guidance of commissural axons toward the floor plate is affected by the absence of Trio. The anterior commissure is absent in Trio-null embryos, and netrin-1/DCC-dependent axonal projections that form the internal capsule and the corpus callosum are defective in the mutants. Taken together, these findings establish Trio as a GEF that mediates netrin-1 signaling in axon outgrowth and guidance through its ability to activate Rac1.

scholarly journals The activation of ezrin–radixin–moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1–induced axon outgrowth

2011 ◽  
Vol 22 (19) ◽  
pp. 3734-3746 ◽  
Author(s):  
Judith Antoine-Bertrand ◽  
Atefeh Ghogha ◽  
Vilayphone Luangrath ◽  
Fiona K. Bedford ◽  
Nathalie Lamarche-Vane
Keyword(s):  
Growth Cone ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Rho Kinase ◽  
Axon Outgrowth ◽  
Actin Binding ◽  
Dependent Manner ◽  
Erm Proteins ◽  
Deleted In Colorectal Cancer ◽  
Ezrin Expression

The receptor Deleted in Colorectal Cancer (DCC) mediates the attractive response of axons to the guidance cue netrin-1 during development. On netrin-1 stimulation, DCC is phosphorylated and induces the assembly of signaling complexes within the growth cone, leading to activation of cytoskeleton regulators, namely the GTPases Rac1 and Cdc42. The molecular mechanisms that link netrin-1/DCC to the actin machinery remain unclear. In this study we seek to demonstrate that the actin-binding proteins ezrin–radixin–moesin (ERM) are effectors of netrin-1/DCC signaling in embryonic cortical neurons. We show that ezrin associates with DCC in a netrin-1–dependent manner. We demonstrate that netrin-1/DCC induces ERM phosphorylation and activation and that the phosphorylation of DCC is required in that context. Moreover, Src kinases and RhoA/Rho kinase activities mediate netrin-1–induced ERM phosphorylation in neurons. We also observed that phosphorylated ERM proteins accumulate in growth cone filopodia, where they colocalize with DCC upon netrin-1 stimulation. Finally, we show that loss of ezrin expression in cortical neurons significantly decreases axon outgrowth induced by netrin-1. Together, our findings demonstrate that netrin-1 induces the formation of an activated ERM/DCC complex in growth cone filopodia, which is required for netrin-1–dependent cortical axon outgrowth.

scholarly journals Presenilin-dependent “γ-Secretase” Processing of Deleted in Colorectal Cancer (DCC)

2003 ◽  
Vol 278 (33) ◽  
pp. 30425-30428 ◽  
Author(s):  
Yoshihito Taniguchi ◽  
Seong-Hun Kim ◽  
Sangram S. Sisodia
Keyword(s):  
Colorectal Cancer ◽  
Deleted In Colorectal Cancer

scholarly journals The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence

2019 ◽  
Vol 25 (2) ◽  
pp. 297-307 ◽  
Author(s):  
Daniel E. Vosberg ◽  
Marco Leyton ◽  
Cecilia Flores
Keyword(s):  
Colorectal Cancer ◽  
Substance Use ◽  
Nervous System ◽  
Axon Guidance ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Guidance System ◽  
Laboratory Animals ◽  
Compelling Evidence ◽  
Deleted In Colorectal Cancer

Abstract Axon guidance molecules direct growing axons toward their targets, assembling the intricate wiring of the nervous system. One of these molecules, Netrin-1, and its receptor, DCC (deleted in colorectal cancer), has profound effects, in laboratory animals, on the adolescent expansion of mesocorticolimbic pathways, particularly dopamine. Now, a rapidly growing literature suggests that (1) these same alterations could occur in humans, and (2) genetic variants in Netrin-1 and DCC are associated with depression, schizophrenia, and substance use. Together, these findings provide compelling evidence that Netrin-1 and DCC influence mesocorticolimbic-related psychopathological states that emerge during adolescence.

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