title: Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB.
abstract: Numerous studies have shown that human endogenous retrovirus W family (HERV-W) envelope gene (env) is related to various diseases but the underlying mechanism has remained poorly understood. Our previous study showed that there was abnormal expression of HERV-W env in sera of patients with schizophrenia. In this paper, we reported that overexpression of the HERV-W env elevated the levels of small conductance Ca(2+)-activated K(+) channel protein 3 (SK3) in human neuroblastoma cells. Using a luciferase reporter system and RNA interference method, we found that functional cAMP response element site was required for the expression of SK3 triggered by HERV-W env. In addition, it was also found that the SK3 channel was activated by HERV-W env. Further study indicated that cAMP response element-binding protein (CREB) was required for the activation of the SK3 channel. Thus, a novel signaling mechanism of how HERV-W env influences neuronal activity and contributes to mental illnesses such as schizophrenia was proposed.
authors.affiliation: Department of Medical Microbiology, School of Medicine, Wuhan University, Wuhan 430071, PR China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: Z C
authors.initials: ZC
authors.lastname: Liu
authors.forename: S J
authors.initials: SJ
authors.lastname: Yin
authors.forename: Y T
authors.initials: YT
authors.lastname: Chen
authors.forename: H L
authors.initials: HL
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Zeng
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Zhu
mesh_terms: D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D020077:Endogenous Retroviruses / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis*; D014759:Viral Envelope Proteins / Q000096:biosynthesis*
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C406328:KCNN3 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014759:Viral Envelope Proteins
keywords: CRE; CREB; Ca(2+)-activated K(+); ENV; HERV; HERV-W; KCa; RT-PCR; SK; SK3; ScyTX; cAMP response element; cAMP response element-binding protein; cAMP response element-binding protein (CREB); env; envelope gene; envelope protein; human endogenous retrovirus; human endogenous retrovirus W family; human endogenous retrovirus W family envelope gene (HERV-W env); pCREB; phosphorylated CREB; reverse transcriptase-polymerase chain reaction; schizophrenia; scyllatoxin; shRNA; short hairpin RNA; small Ca(2+)-activated K(+); small conductance Ca(2+)-activated K(+) channel protein 3; small conductance Ca(2+)-activated K(+) channel protein 3 (SK3)