title: KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis.
abstract: Weak electric fields guide cell migration, known as galvanotaxis/electrotaxis. The sensor(s) cells use to detect the fields remain elusive. Here we perform a large-scale screen using an RNAi library targeting ion transporters in human cells. We identify 18 genes that show either defective or increased galvanotaxis after knockdown. Knockdown of the KCNJ15 gene (encoding inwardly rectifying K(+) channel Kir4.2) specifically abolishes galvanotaxis, without affecting basal motility and directional migration in a monolayer scratch assay. Depletion of cytoplasmic polyamines, highly positively charged small molecules that regulate Kir4.2 function, completely inhibits galvanotaxis, whereas increase of intracellular polyamines enhances galvanotaxis in a Kir4.2-dependent manner. Expression of a polyamine-binding defective mutant of KCNJ15 significantly decreases galvanotaxis. Knockdown or inhibition of KCNJ15 prevents phosphatidylinositol 3,4,5-triphosphate (PIP3) from distributing to the leading edge. Taken together these data suggest a previously unknown two-molecule sensing mechanism in which KCNJ15/Kir4.2 couples with polyamines in sensing weak electric fields.
authors.affiliation: Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California Davis, Sacramento, California 95817, USA.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nakajima
authors.affiliation: Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California Davis, Sacramento, California 95817, USA.|Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California Davis, Sacramento, California 95817, USA.
authors.forename: Yao-Hui
authors.initials: YH
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, University of California Davis, Davis, California 95616, USA.
authors.forename: Bence
authors.initials: B
authors.lastname: Hegyi
authors.affiliation: Bioelectromagnetics Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Qunli
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California 95616, USA.|Department of Ophthalmology &Vision Science, School of Medicine, University of California Davis, Sacramento, California 95817, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: J Victor
authors.initials: JV
authors.lastname: Small
authors.affiliation: Department of Pharmacology, University of California Davis, Davis, California 95616, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen-Izu
authors.affiliation: Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California Davis, Sacramento, California 95817, USA.|Department of Biochemistry and Molecular Medicine, University of California at Davis, Sacramento, California 95616, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Izumiya
authors.affiliation: IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.affiliation: Department of Dermatology, Institute for Regenerative Cures, School of Medicine, University of California Davis, Sacramento, California 95817, USA.|Department of Ophthalmology &Vision Science, School of Medicine, University of California Davis, Sacramento, California 95817, USA.
authors.forename: Min
authors.identifier: http://orcid.org/0000-0002-2500-3035
authors.initials: M
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D004560:Electricity; D006801:Humans; D017136:Ion Transport; D011073:Polyamines / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*
chemical_list: C489469:Kir4.2 channel; D011073:Polyamines; D024661:Potassium Channels, Inwardly Rectifying