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

eLife

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[1] Department 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 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 States;Department 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 States;Department 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 States;Department 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 States;Department 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 States;Jan 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 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 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;

关键词: neurexophilin4;    α-neurexin;    GABAA receptors;    cerebellum;    Golgi cells;    Mouse;   

DOI  :  10.7554/eLife.46773

来源: publisher

【 摘 要 】

10.7554/eLife.46773.001Neurexophilins 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.

【 授权许可】

CC BY