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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4895136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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