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Slitrk1 is localized to excitatory synapses and promotes their development

Following the migration of the axonal growth cone to its target area, the initial axo-dendritic contact needs to be transformed into a functional synapse. This multi-step process relies on overlapping but distinct combinations of molecules that confer synaptic identity. Slitrk molecules are transmem...

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Autores principales: Beaubien, François, Raja, Reesha, Kennedy, Timothy E., Fournier, Alyson E., Cloutier, Jean-François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895136/
https://www.ncbi.nlm.nih.gov/pubmed/27273464
http://dx.doi.org/10.1038/srep27343
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author Beaubien, François
Raja, Reesha
Kennedy, Timothy E.
Fournier, Alyson E.
Cloutier, Jean-François
author_facet Beaubien, François
Raja, Reesha
Kennedy, Timothy E.
Fournier, Alyson E.
Cloutier, Jean-François
author_sort Beaubien, François
collection PubMed
description Following the migration of the axonal growth cone to its target area, the initial axo-dendritic contact needs to be transformed into a functional synapse. This multi-step process relies on overlapping but distinct combinations of molecules that confer synaptic identity. Slitrk molecules are transmembrane proteins that are highly expressed in the central nervous system. We found that two members of the Slitrk family, Slitrk1 and Slitrk2, can regulate synapse formation between hippocampal neurons. Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses. Overexpression of Slitrk1 and Slitrk2 in hippocampal neurons increased the number of synaptic contacts on these neurons. Furthermore, decreased expression of Slitrk1 in hippocampal neurons led to a reduction in the number of excitatory, but not inhibitory, synapses formed in hippocampal neuron cultures. In addition, we demonstrate that different leucine rich repeat domains of the extracellular region of Slitrk1 are necessary to mediate interactions with Slitrk binding partners of the LAR receptor protein tyrosine phosphatase family, and to promote dimerization of Slitrk1. Altogether, our results demonstrate that Slitrk family proteins regulate synapse formation.
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spelling pubmed-48951362016-06-10 Slitrk1 is localized to excitatory synapses and promotes their development Beaubien, François Raja, Reesha Kennedy, Timothy E. Fournier, Alyson E. Cloutier, Jean-François Sci Rep Article Following the migration of the axonal growth cone to its target area, the initial axo-dendritic contact needs to be transformed into a functional synapse. This multi-step process relies on overlapping but distinct combinations of molecules that confer synaptic identity. Slitrk molecules are transmembrane proteins that are highly expressed in the central nervous system. We found that two members of the Slitrk family, Slitrk1 and Slitrk2, can regulate synapse formation between hippocampal neurons. Slitrk1 is enriched in postsynaptic fractions and is localized to excitatory synapses. Overexpression of Slitrk1 and Slitrk2 in hippocampal neurons increased the number of synaptic contacts on these neurons. Furthermore, decreased expression of Slitrk1 in hippocampal neurons led to a reduction in the number of excitatory, but not inhibitory, synapses formed in hippocampal neuron cultures. In addition, we demonstrate that different leucine rich repeat domains of the extracellular region of Slitrk1 are necessary to mediate interactions with Slitrk binding partners of the LAR receptor protein tyrosine phosphatase family, and to promote dimerization of Slitrk1. Altogether, our results demonstrate that Slitrk family proteins regulate synapse formation. Nature Publishing Group 2016-06-07 /pmc/articles/PMC4895136/ /pubmed/27273464 http://dx.doi.org/10.1038/srep27343 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Beaubien, François
Raja, Reesha
Kennedy, Timothy E.
Fournier, Alyson E.
Cloutier, Jean-François
Slitrk1 is localized to excitatory synapses and promotes their development
title Slitrk1 is localized to excitatory synapses and promotes their development
title_full Slitrk1 is localized to excitatory synapses and promotes their development
title_fullStr Slitrk1 is localized to excitatory synapses and promotes their development
title_full_unstemmed Slitrk1 is localized to excitatory synapses and promotes their development
title_short Slitrk1 is localized to excitatory synapses and promotes their development
title_sort slitrk1 is localized to excitatory synapses and promotes their development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895136/
https://www.ncbi.nlm.nih.gov/pubmed/27273464
http://dx.doi.org/10.1038/srep27343
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