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The actin-binding protein Canoe/AF-6 forms a complex with Robo and is required for Slit-Robo signaling during axon pathfinding at the CNS midline

Slováková, J., Speicher, S., Sánchez-Soriano, N., Prokop, A., Carmena, A

J. Neurosci. 2012;32(29):10035-10044.

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Abstract

Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study the mechanisms underlying this process is the axon decision of whether or not to cross the midline in the Drosophila CNS. An essential regulator of that decision is the well-conserved Slit-Robo signaling pathway. Slit guidance cues act through Robo receptors to repel axons from the midline. Despite good progress in our knowledge about these proteins, the intracellular mechanisms associated with Robo function remain poorly defined. In this work, we found that the scaffolding protein Canoe (Cno), the Drosophila orthologue of AF-6/Afadin, is essential for Slit-Robo signaling. Cno is expressed along longitudinal axonal pioneer tracks, and longitudinal Robo/Fasciclin2-positive axons aberrantly cross the midline in cno mutant embryos. cno mutant primary neurons show a significant reduction of Robo localized in growth cone filopodia and Cno forms a complex with Robo in vivo. Moreover, the commissureless (comm) phenotype (i.e. lack of commissures due to constitutive surface presentation of Robo in all neurons) is suppressed in comm, cno double mutant embryos. Specific genetic interactions between cno, slit, robo and genes encoding other components of the Robo pathway, such as Neurexin-IV, Syndecan and Rac GTPases, further confirm that Cno functionally interacts with the Slit-Robo pathway. Our data argue that Cno is a novel regulator of the Slit-Robo signaling pathway, crucial for regulating the subcellular localization of Robo and for transducing its signaling to the actin cytoskeleton during axon guidance at the midline. [full text/PDF: http://www.jneurosci.org/content/32/29/10035.long]

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Published date:
Journal title:
Volume:
32
Issue:
29
Start page:
10035
End page:
10044
Digital Object Identifier:
10.1523/JNEUROSCI.6342-11.2012
Related website(s):
  • Related website http://www.jneurosci.org/content/32/29/10035.longhttp://www.ncbi.nlm.nih.gov/pubmed/22815517
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Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:161941
Created by:
Prokop, Andreas
Created:
29th May, 2012, 17:34:14
Last modified by:
Prokop, Andreas
Last modified:
27th October, 2015, 12:32:56

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