title: ASIC1 promotes differentiation of neuroblastoma by negatively regulating Notch signaling pathway.
abstract: In neurons, up-regulation of Notch activity either inhibits neurite extension or causes retraction of neurites. Conversely, inhibition of Notch1 facilitates neurite extension. Acid-sensing ion channels (ASICs) are a family of proton-gated cation channels, which play critical roles in synaptic plasticity, learning and memory and spine morphogenesis. Our pilot proteomics data from ASIC1a knock out mice implicated that ASIC1a may play a role in regulating Notch signaling, therefore, we explored whether or not ASIC1a regulates neurite growth during neuronal development through Notch signaling. In this study, we determined the effects of ASIC1a on neurite growth in a mouse neuroblastoma cell line, NS20Y cells, by modulating ASIC1a expression. We also determined the relationship between ASIC1a and Notch signaling on neuronal differentiation. Our results showed that down-regulation of ASIC1a in NS20Y cells inhibits CPT-cAMP induced neurite growth, while over expression of ASIC1a promotes its growth. In addition, down-regulation of ASIC1a increased the expression of Notch1 and its target gene Survivin while inhibitor of Notch significantly prevented the neurite extension induced by ASIC1a in NS20Y cells. These data indicate that Notch1 signaling may be required for ASIC1a-mediated neurite growth and neuronal differentiation.
authors.affiliation: Department of Microbiology, Biochemistry & Immunology, Atlanta, GA 30310, USA.
authors.forename: Mingli
authors.initials: M
authors.lastname: Liu
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Tiandong
authors.initials: T
authors.lastname: Leng
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: An
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA.
authors.forename: Shanchun
authors.initials: S
authors.lastname: Guo
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Xiong
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004151:Dipeptides; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071446:Neuronal Outgrowth / Q000187:drug effects; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000242:Cyclic AMP
keywords: ASIC1a; NS20Y; Notch; neurite growth