Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.

The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be...

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Main Authors: Maryam Alavi, Minmin Song, Gracie L Andrews King, Taylor Gillis, Robert Propst, Matthew Lamanuzzi, Adam Bousum, Amanda Miller, Ryan Allen, Thomas Kidd
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-09-01
Series:PLoS Biology
Online Access:http://europepmc.org/articles/PMC5031454?pdf=render
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spelling doaj-9f0a630a718847e8bc97bef647cda4b32021-07-02T08:00:08ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852016-09-01149e100256010.1371/journal.pbio.1002560Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.Maryam AlaviMinmin SongGracie L Andrews KingTaylor GillisRobert PropstMatthew LamanuzziAdam BousumAmanda MillerRyan AllenThomas KiddThe Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins.http://europepmc.org/articles/PMC5031454?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Maryam Alavi
Minmin Song
Gracie L Andrews King
Taylor Gillis
Robert Propst
Matthew Lamanuzzi
Adam Bousum
Amanda Miller
Ryan Allen
Thomas Kidd
spellingShingle Maryam Alavi
Minmin Song
Gracie L Andrews King
Taylor Gillis
Robert Propst
Matthew Lamanuzzi
Adam Bousum
Amanda Miller
Ryan Allen
Thomas Kidd
Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
PLoS Biology
author_facet Maryam Alavi
Minmin Song
Gracie L Andrews King
Taylor Gillis
Robert Propst
Matthew Lamanuzzi
Adam Bousum
Amanda Miller
Ryan Allen
Thomas Kidd
author_sort Maryam Alavi
title Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
title_short Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
title_full Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
title_fullStr Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
title_full_unstemmed Dscam1 Forms a Complex with Robo1 and the N-Terminal Fragment of Slit to Promote the Growth of Longitudinal Axons.
title_sort dscam1 forms a complex with robo1 and the n-terminal fragment of slit to promote the growth of longitudinal axons.
publisher Public Library of Science (PLoS)
series PLoS Biology
issn 1544-9173
1545-7885
publishDate 2016-09-01
description The Slit protein is a major midline repellent for central nervous system (CNS) axons. In vivo, Slit is proteolytically cleaved into N- and C-terminal fragments, but the biological significance of this is unknown. Analysis in the Drosophila ventral nerve cord of a slit allele (slit-UC) that cannot be cleaved revealed that midline repulsion is still present but longitudinal axon guidance is disrupted, particularly across segment boundaries. Double mutants for the Slit receptors Dscam1 and robo1 strongly resemble the slit-UC phenotype, suggesting they cooperate in longitudinal axon guidance, and through biochemical approaches, we found that Dscam1 and Robo1 form a complex dependent on Slit-N. In contrast, Robo1 binding alone shows a preference for full-length Slit, whereas Dscam1 only binds Slit-N. Using a variety of transgenes, we demonstrated that Dscam1 appears to modify the output of Robo/Slit complexes so that signaling is no longer repulsive. Our data suggest that the complex is promoting longitudinal axon growth across the segment boundary. The ability of Dscam1 to modify the output of other receptors in a ligand-dependent fashion may be a general principle for Dscam proteins.
url http://europepmc.org/articles/PMC5031454?pdf=render
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