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Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions

Neurexophilins are secreted neuropeptide-like glycoproteins, and neurexophilin1 and neurexophilin3 are ligands for the presynaptic cell adhesion molecule α-neurexin. Neurexophilins are more selectively expressed in the brain than α-neurexins, however, which led us to ask whether neurexophilins modul...

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Autores principales: Meng, Xiangling, McGraw, Christopher M, Wang, Wei, Jing, Junzhan, Yeh, Szu-Ying, Wang, Li, Lopez, Joanna, Brown, Amanda M, Lin, Tao, Chen, Wu, Xue, Mingshan, Sillitoe, Roy V, Jiang, Xiaolong, Zoghbi, Huda Y
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763262/
https://www.ncbi.nlm.nih.gov/pubmed/31524598
http://dx.doi.org/10.7554/eLife.46773
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author Meng, Xiangling
McGraw, Christopher M
Wang, Wei
Jing, Junzhan
Yeh, Szu-Ying
Wang, Li
Lopez, Joanna
Brown, Amanda M
Lin, Tao
Chen, Wu
Xue, Mingshan
Sillitoe, Roy V
Jiang, Xiaolong
Zoghbi, Huda Y
author_facet Meng, Xiangling
McGraw, Christopher M
Wang, Wei
Jing, Junzhan
Yeh, Szu-Ying
Wang, Li
Lopez, Joanna
Brown, Amanda M
Lin, Tao
Chen, Wu
Xue, Mingshan
Sillitoe, Roy V
Jiang, Xiaolong
Zoghbi, Huda Y
author_sort Meng, Xiangling
collection PubMed
description Neurexophilins are secreted neuropeptide-like glycoproteins, and neurexophilin1 and neurexophilin3 are ligands for the presynaptic cell adhesion molecule α-neurexin. Neurexophilins are more selectively expressed in the brain than α-neurexins, however, which led us to ask whether neurexophilins modulate the function of α-neurexin in a context-specific manner. We characterized the expression and function of neurexophilin4 in mice and found it to be expressed in subsets of neurons responsible for feeding, emotion, balance, and movement. Deletion of Neurexophilin4 caused corresponding impairments, most notably in motor learning and coordination. We demonstrated that neurexophilin4 interacts with α-neurexin and GABA(A)Rs in the cerebellum. Loss of Neurexophilin4 impaired cerebellar Golgi-granule inhibitory neurotransmission and synapse number, providing a partial explanation for the motor learning and coordination deficits observed in the Neurexophilin4 null mice. Our data illustrate how selectively expressed Neurexophilin4, an α-neurexin ligand, regulates specific synapse function and modulates cerebellar motor control.
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spelling pubmed-67632622019-10-02 Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions Meng, Xiangling McGraw, Christopher M Wang, Wei Jing, Junzhan Yeh, Szu-Ying Wang, Li Lopez, Joanna Brown, Amanda M Lin, Tao Chen, Wu Xue, Mingshan Sillitoe, Roy V Jiang, Xiaolong Zoghbi, Huda Y eLife Neuroscience Neurexophilins are secreted neuropeptide-like glycoproteins, and neurexophilin1 and neurexophilin3 are ligands for the presynaptic cell adhesion molecule α-neurexin. Neurexophilins are more selectively expressed in the brain than α-neurexins, however, which led us to ask whether neurexophilins modulate the function of α-neurexin in a context-specific manner. We characterized the expression and function of neurexophilin4 in mice and found it to be expressed in subsets of neurons responsible for feeding, emotion, balance, and movement. Deletion of Neurexophilin4 caused corresponding impairments, most notably in motor learning and coordination. We demonstrated that neurexophilin4 interacts with α-neurexin and GABA(A)Rs in the cerebellum. Loss of Neurexophilin4 impaired cerebellar Golgi-granule inhibitory neurotransmission and synapse number, providing a partial explanation for the motor learning and coordination deficits observed in the Neurexophilin4 null mice. Our data illustrate how selectively expressed Neurexophilin4, an α-neurexin ligand, regulates specific synapse function and modulates cerebellar motor control. eLife Sciences Publications, Ltd 2019-09-16 /pmc/articles/PMC6763262/ /pubmed/31524598 http://dx.doi.org/10.7554/eLife.46773 Text en © 2019, Meng et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Meng, Xiangling
McGraw, Christopher M
Wang, Wei
Jing, Junzhan
Yeh, Szu-Ying
Wang, Li
Lopez, Joanna
Brown, Amanda M
Lin, Tao
Chen, Wu
Xue, Mingshan
Sillitoe, Roy V
Jiang, Xiaolong
Zoghbi, Huda Y
Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title_full Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title_fullStr Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title_full_unstemmed Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title_short Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
title_sort neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763262/
https://www.ncbi.nlm.nih.gov/pubmed/31524598
http://dx.doi.org/10.7554/eLife.46773
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