Cargando…

Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice

Synapse assembly requires transsynaptic signals between the pre- and postsynapse(1), but the understanding of essential organizational molecules remains incomplete(2). Teneurins are conserved, EGF-repeat containing transmembrane proteins with large extracellular domains(3). Here we show that two Dro...

Descripción completa

Detalles Bibliográficos
Autores principales: Mosca, Timothy J., Hong, Weizhe, Dani, Vardhan S., Favaloro, Vincenzo, Luo, Liqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326183/
https://www.ncbi.nlm.nih.gov/pubmed/22426000
http://dx.doi.org/10.1038/nature10923
_version_ 1782229502711037952
author Mosca, Timothy J.
Hong, Weizhe
Dani, Vardhan S.
Favaloro, Vincenzo
Luo, Liqun
author_facet Mosca, Timothy J.
Hong, Weizhe
Dani, Vardhan S.
Favaloro, Vincenzo
Luo, Liqun
author_sort Mosca, Timothy J.
collection PubMed
description Synapse assembly requires transsynaptic signals between the pre- and postsynapse(1), but the understanding of essential organizational molecules remains incomplete(2). Teneurins are conserved, EGF-repeat containing transmembrane proteins with large extracellular domains(3). Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic while Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization transsynaptically and cell-autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with α-spectrin. Genetic analyses of teneurin and neuroligin reveal their differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates specific motoneuron-muscle target selection. Our study identifies the Teneurins as a key bi-directional transsynaptic signal in general synapse organization, and demonstrates that such a molecule can also regulate target selection.
format Online
Article
Text
id pubmed-3326183
institution National Center for Biotechnology Information
language English
publishDate 2012
record_format MEDLINE/PubMed
spelling pubmed-33261832012-10-12 Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice Mosca, Timothy J. Hong, Weizhe Dani, Vardhan S. Favaloro, Vincenzo Luo, Liqun Nature Article Synapse assembly requires transsynaptic signals between the pre- and postsynapse(1), but the understanding of essential organizational molecules remains incomplete(2). Teneurins are conserved, EGF-repeat containing transmembrane proteins with large extracellular domains(3). Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic while Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization transsynaptically and cell-autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with α-spectrin. Genetic analyses of teneurin and neuroligin reveal their differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates specific motoneuron-muscle target selection. Our study identifies the Teneurins as a key bi-directional transsynaptic signal in general synapse organization, and demonstrates that such a molecule can also regulate target selection. 2012-03-18 /pmc/articles/PMC3326183/ /pubmed/22426000 http://dx.doi.org/10.1038/nature10923 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mosca, Timothy J.
Hong, Weizhe
Dani, Vardhan S.
Favaloro, Vincenzo
Luo, Liqun
Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title_full Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title_fullStr Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title_full_unstemmed Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title_short Transsynaptic Teneurin Signaling in Neuromuscular Synapse Organization and Target Choice
title_sort transsynaptic teneurin signaling in neuromuscular synapse organization and target choice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3326183/
https://www.ncbi.nlm.nih.gov/pubmed/22426000
http://dx.doi.org/10.1038/nature10923
work_keys_str_mv AT moscatimothyj transsynapticteneurinsignalinginneuromuscularsynapseorganizationandtargetchoice
AT hongweizhe transsynapticteneurinsignalinginneuromuscularsynapseorganizationandtargetchoice
AT danivardhans transsynapticteneurinsignalinginneuromuscularsynapseorganizationandtargetchoice
AT favalorovincenzo transsynapticteneurinsignalinginneuromuscularsynapseorganizationandtargetchoice
AT luoliqun transsynapticteneurinsignalinginneuromuscularsynapseorganizationandtargetchoice