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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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/46773 |
| _version_ | 1818026960793632768 |
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| author | Xiangling Meng Christopher M McGraw Wei Wang Junzhan Jing Szu-Ying Yeh Li Wang Joanna Lopez Amanda M Brown Tao Lin Wu Chen Mingshan Xue Roy V Sillitoe Xiaolong Jiang Huda Y Zoghbi |
| author_facet | Xiangling Meng Christopher M McGraw Wei Wang Junzhan Jing Szu-Ying Yeh Li Wang Joanna Lopez Amanda M Brown Tao Lin Wu Chen Mingshan Xue Roy V Sillitoe Xiaolong Jiang Huda Y Zoghbi |
| author_sort | Xiangling Meng |
| collection | DOAJ |
| 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 GABAARs 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. |
| first_indexed | 2024-12-10T04:40:19Z |
| format | Article |
| id | doaj.art-ee4b5412662f4e2b8cf2bc5b400ed7db |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:40:19Z |
| publishDate | 2019-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ee4b5412662f4e2b8cf2bc5b400ed7db2022-12-22T02:01:55ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.46773Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functionsXiangling Meng0https://orcid.org/0000-0002-3528-4037Christopher M McGraw1Wei Wang2Junzhan Jing3Szu-Ying Yeh4https://orcid.org/0000-0003-4506-5652Li Wang5Joanna Lopez6Amanda M Brown7Tao Lin8Wu Chen9Mingshan Xue10https://orcid.org/0000-0003-1463-8884Roy V Sillitoe11https://orcid.org/0000-0002-6177-6190Xiaolong Jiang12Huda Y Zoghbi13https://orcid.org/0000-0002-0700-3349Department of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United StatesJan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; Department of Pathology and Immunology, Baylor College of Medicine, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, United States; Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, United States; Program in Developmental Biology, Baylor College of Medicine, Houston, United States; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United StatesNeurexophilins 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 GABAARs 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.https://elifesciences.org/articles/46773neurexophilin4α-neurexinGABAA receptorscerebellumGolgi cells |
| spellingShingle | Xiangling Meng Christopher M McGraw Wei Wang Junzhan Jing Szu-Ying Yeh Li Wang Joanna Lopez Amanda M Brown Tao Lin Wu Chen Mingshan Xue Roy V Sillitoe Xiaolong Jiang Huda Y Zoghbi Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions eLife neurexophilin4 α-neurexin GABAA receptors cerebellum Golgi cells |
| 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 | neurexophilin4 α-neurexin GABAA receptors cerebellum Golgi cells |
| url | https://elifesciences.org/articles/46773 |
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