2015/10/09 by Kenichi Nakajima, Kan Zhu, Yaohui Sun +8 · 1 citation
Biochemistry, Genetics and Molecular Biology · Agricultural and Biological Sciences · Chemistry · #Planarian Biology and Electrostimulation #Ion channel regulation and function #Plant and Biological Electrophysiology Studies #Gene knockdown #Cell biology #Extracellular #Mutant #HEK 293 cells #Intracellular #Motility #Biology #Biophysics #Molecular biology #Chemistry #Biochemistry #Gene
paper · pdf · doi:10.1038/ncomms9532
openalex publication_date 2015/10/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/05
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.