Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,micro...Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,microglia,and neurons.However,the distribution and function of Panx 1 in the peripheral nervous system are not clear.Blocking the function of Panx 1 pharmacologically(carbenoxolone and probenecid)or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release.Treatment of Schwann cells with a Ras homolog family member(Rho)GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents,such as nocodazole or cytochalasin D,revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton.These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement.This study was approved by the Animal Ethics Committee of Nantong University,China(No.S20180806-002)on August 5,2018.展开更多
Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were e...Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion （DRG） neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.展开更多
基金This study was supported by the National Natural Science Foundation of China,Nos.31900718(to ZYW),31872773(to GC)the National Key Research and Development Program of China,No.2017YFA0104704(to GC)+2 种基金Basic Research Program of the Education Department of Jiangsu Province of China,Nos.19KJB180024(to ZYW),18KJB180020(to WXS)Postdoctoral Science Foundation of China,No.2019M651925(to ZYW),Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program of China,No.201810304031Z(to YJD)Six Talent Peaks Project in Jiangsu Province of China,No.WSN-007(to WXS).
文摘Pannexin 1(Panx 1),as a large-pore membrane channel,is highly permeable to ATP and other signaling molecules.Previous studies have demonstrated the expression of Panx 1 in the nervous system,including astrocytes,microglia,and neurons.However,the distribution and function of Panx 1 in the peripheral nervous system are not clear.Blocking the function of Panx 1 pharmacologically(carbenoxolone and probenecid)or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release.Treatment of Schwann cells with a Ras homolog family member(Rho)GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents,such as nocodazole or cytochalasin D,revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton.These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement.This study was approved by the Animal Ethics Committee of Nantong University,China(No.S20180806-002)on August 5,2018.
基金supported by the National Natural Science Foundation of China,No.31071251,81471255,and 81471259a grant from the Ministry of Science and Technology of China(973 Program),No.2014CB542202+2 种基金a grant from the Basic Research Program of Education Department of Jiangsu Province,China,No.14KJA310004a grant from the Natural Science Research Project of Nantong Science and Technology Bureau,China,No.HS2013014a grant from the Natural Science Research Project of Nantong University,China,No.13Z008
文摘Myelination of Schwann cells in the peripheral nervous system is an intricate process involving myelin protein trafficking. Recently, the role and mechanism of the endosomal/lysosomal system in myelin formation were emphasized. Our previous results demonstrated that a small GTPase Rab27a regulates lysosomal exocytosis and myelin protein trafficking in Schwann cells. In this present study, we established a dorsal root ganglion （DRG） neuron and Schwann cell co-culture model to identify the signals associated with Rab27a during myelination. First, Slp2-a, as the Rab27a effector, was endogenously expressed in Schwann cells. Second, Rab27a expression significantly increased during Schwann cell myelination. Finally, Rab27a and Slp2-a silencing in Schwann cells not only reduced myelin protein expression, but also impaired formation of myelin-like membranes in DRG neuron and Schwann cell co-cultures. Our findings suggest that the Rab27a/ Slp2-a complex affects Schwann cell myelination in vitro.
