Spontaneous and electric feld-controlled front-rear polarization of human keratinocytes

Deniz Saltukoglu, Julian Grünewald, Nico Strohmeyer, Robert Bensch, Maximilian H. Ulbrich, Olaf Ronneberger, Matias Simons

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

It has long been known that electrical felds (EFs) are able to infuence the direction of migrating cells, a process commonly referred to as electrotaxis or galvanotaxis. Most studies have focused on migrating cells equipped with an existing polarity before EF application, making it diffcult to delineate EF-specifc pathways. Here we study the initial events in front-rear organization of spreading keratinocytes to dissect the molecular requirements for random and EF-controlled polarization. We fnd that Arp2/3-dependent protrusive forces and Rac1/Cdc42 activity were generally required for both forms of polarization but were dispensable for controlling the direction of EF-controlled polarization. By contrast, we found a crucial role for extracellular pH as well as G protein coupled-receptor (GPCR) or purinergic signaling in the control of directionality. The normal direction of polarization toward the cathode was reverted by lowering extracellular pH. Polarization toward the anode was also seen at neutral pH when GPCR or purinergic signaling was inhibited. However, the stepwise increase of extracellular pH in this scenario led to restoration of cathodal polarization. Overall our work puts forward a model in which the EF uses distinct polarization pathways. The cathodal pathway involves GPCR/purinergic signaling and is dominant over the anodal pathway at neutral pH.

Original languageEnglish
Pages (from-to)4373-4386
Number of pages14
JournalMolecular Biology of the Cell
Volume26
Issue number24
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

Fingerprint

Dive into the research topics of 'Spontaneous and electric feld-controlled front-rear polarization of human keratinocytes'. Together they form a unique fingerprint.

Cite this