title: Co-expression of mouse TMEM63A, TMEM63B and TMEM63C confers hyperosmolarity activated ion currents in HEK293 cells.
abstract: Osmoreception is essential for systemic osmoregulation, a process to stabilize the tonicity and volume of the extracellular fluid through regulating the ingestive behaviour, sympathetic outflow and renal function. The sensation of osmotic changes by osmoreceptor neurons is mediated by ion channels that detect the change of osmolarity in extracellular fluid. However, the molecular identity of these channels remains mysterious. AtCSC1and OSCA1,two closely related paralogues from Arabidopsis, have been demonstrated to form hyperosmolarity activated ion channels, which makes their mammalian orthologues-the members of TMEM63 proteins, possible candidates for osmoreceptor transduction channel. To test this possibility, we cloned the cDNAs of all the three members of the mouse TMEM63 family, TMEM63A, TMEM63B and TMEM63C from the mRNA from mouse brain. When all of the three subtypes of TMEM63 proteins were co-expressed in HEK293 cells, we recorded membrane currents evoked by hypertonic stimulation in these cells. However, the cells expressing the combinations of any two subtypes of TMEM63 proteins could not exhibit any hyperosmolarity evoked currents. Thus, all the three members of TMEM63 proteins are required to constitute a hyperosmolarity activated ion channel. We propose that the TMEM63 proteins may serve as an osmolarity sensitive ion channel for the osmoreception. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Department of Anesthesiology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Yan
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yuanhu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D006982:Hypertonic Solutions / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009994:Osmolar Concentration; D010802:Phylogeny
chemical_list: D006982:Hypertonic Solutions; D007473:Ion Channels; D008565:Membrane Proteins
keywords: TMEM63A; TMEM63B; TMEM63C; ion channel; osmoreceptor; osmoregulation