KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis

Kenichi Nakajima, Kan Zhu, Yao Hui Sun, Bence Hegyi, Qunli Zeng, Christopher J Murphy, J. Victor Small, Ye Chen-Izu, Yoshihiro Izumiya, Josef M. Penninger, Min Zhao

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 (PIP 3) 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.

Original languageEnglish (US)
Article number8532
JournalNature Communications
Volume6
DOIs
StatePublished - Oct 9 2015

Fingerprint

Polyamines
genes
Electric fields
transporter
locomotion
distributing
electric fields
leading edges
cells
molecules
coding
depletion
Inwardly Rectifying Potassium Channel
Molecules
Gene encoding
sensors
Gene Knockdown Techniques
Monolayers
Assays
ions

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

KCNJ15/Kir4.2 couples with polyamines to sense weak extracellular electric fields in galvanotaxis. / Nakajima, Kenichi; Zhu, Kan; Sun, Yao Hui; Hegyi, Bence; Zeng, Qunli; Murphy, Christopher J; Small, J. Victor; Chen-Izu, Ye; Izumiya, Yoshihiro; Penninger, Josef M.; Zhao, Min.

In: Nature Communications, Vol. 6, 8532, 09.10.2015.

Research output: Contribution to journalArticle

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