期刊
CELLULAR AND MOLECULAR LIFE SCIENCES
卷 71, 期 23, 页码 4653-4663出版社
SPRINGER BASEL AG
DOI: 10.1007/s00018-014-1632-1
关键词
NHE3; PKC eta; Resting membrane potential; Wound healing; Electric fields
资金
- German Research Foundation (DFG) [OE541/1-1]
- MeDDrive-Grant from the Medical Faculty of Technical University of Dresden [Ozkucur_60.246]
- Royal Society URF award [UF051616]
- European Research Council StG grant [243261]
- National Science Foundation [MCB-0951199]
- California Institute of Regenerative Medicine Research [RB1-01417]
- Research to Prevent Blindness to University of California, Davis, Ophthalmology
- NIH-NEI [R01-EY-019101]
- The British Council [GII112] Funding Source: researchfish
Endogenous electric fields (EF) may provide an overriding cue for directional cell migration during wound closure. Perceiving a constant direction requires active sodium-hydrogen exchanger (pNHE3) at the leading edge of HEK 293 cells but its activation mechanism is not yet fully understood. Because protein kinase C (PKC) is required in electrotaxis, we asked whether NHE3 is activated by PKC during wound healing. Using pharmacological (pseudosubstrate and edelfosine) inhibition, we showed that inhibition of PKC eta isoform impairs directional cell migration in HEK 293 cells in the presence of a persistent directional cue (0.25-0.3 V/mm of EF for 2 h). Further, we found that pNHE3 forms complexes with both PKC eta and gamma-tubulin, suggesting that these molecules may regulate the microtubule-organizing center. In addition, cellular pNHE3 content was reduced significantly when PKC eta was inhibited during directional cell migration. Taken together, these data suggest that PKC eta-dependent phosphorylation of NHE3 and the formation of pNHE3/PKC eta/gamma-tubulin complexes at the leading edge of the cell are required for directional cell migration in an EF.
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