Molecular Chaperone Calnexin Regulates the Function ofDrosophilaSodium Channel Paralytic.
Neuronal activity mediated by voltage-gated channels provides the basis for higher-order behavioral tasks that orchestrate life. Chaperone-mediated regulation, one of the major means to control protein quality and function, is an essential route for controlling channel activity. Here we present evidence thatDrosophilaER chaperone Calnexin colocalizes and interacts with the α subunit of sodium channel Paralytic. Co-immunoprecipitation analysis indicates that Calnexin interacts with Paralytic protein variants that contain glycosylation sites Asn313, 325, 343, 1463, and 1482. Downregulation of Calnexin expression results in a decrease in Paralytic protein levels, whereas overexpression of the Calnexin C-terminal calcium-binding domain triggers an increase reversely. Genetic analysis using adult climbing, seizure-induced paralysis, and neuromuscular junction indicates that lack of Calnexin expression enhances Paralytic-mediated locomotor deficits, suppresses Paralytic-mediated ghost bouton formation, and regulates minature excitatory junction potentials (mEJP) frequency and latency time. Taken together, our findings demonstrate a need for chaperone-mediated regulation on channel activity during locomotor control, providing the molecular basis for channlopathies such as epilepsy.
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Xi
X
Xiao
Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Institute of Intervention Vessel, Shanghai 10th People's Hospital, Tongji University Shanghai, China.
Changyan
C
Chen
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Tian-Ming
TM
Yu
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Jiayao
J
Ou
Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University Nanjing, China.
Menglong
M
Rui
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Yuanfen
Y
Zhai
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Yijing
Y
He
Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Institute of Intervention Vessel, Shanghai 10th People's Hospital, Tongji University Shanghai, China.
Lei
L
Xue
Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of MedicineShanghai, China; Department of Anatomy and Neurobiology, Tongji University School of MedicineShanghai, China.
Margaret S
MS
Ho
Calnexin chaperone; NMJ synaptogenesis; locomotor behavior; paralytic; sodium channel