TY - JOUR TI - Neurexophilin4 is a selectively expressed α-neurexin ligand that modulates specific cerebellar synapses and motor functions AU - Meng, Xiangling AU - McGraw, Christopher M AU - Wang, Wei AU - Jing, Junzhan AU - Yeh, Szu-Ying AU - Wang, Li AU - Lopez, Joanna AU - Brown, Amanda M AU - Lin, Tao AU - Chen, Wu AU - Xue, Mingshan AU - Sillitoe, Roy V AU - Jiang, Xiaolong AU - Zoghbi, Huda Y A2 - Monteggia, Lisa M A2 - Dulac, Catherine A2 - Hatten, Mary E VL - 8 PY - 2019 DA - 2019/09/16 SP - e46773 C1 - eLife 2019;8:e46773 DO - 10.7554/eLife.46773 UR - https://doi.org/10.7554/eLife.46773 AB - 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. KW - neurexophilin4 KW - α-neurexin KW - GABAA receptors KW - cerebellum KW - Golgi cells JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -