NHE3 phosphorylation via PKCη marks the polarity and orientation of directionally migrating cells
详细信息 查看全文
- 作者：Nurdan ?zkucur (1) (2) (3)
Bing Song (2) (4)
Sharanya Bola (1)
Lei Zhang (2) (5)
Brian Reid (2)
Guo Fu (6)
Richard H. W. Funk (1) (7)
Min Zhao (2) - 关键词：NHE3 ; PKCη ; Resting membrane potential ; Wound healing ; Electric fields
- 刊名：Cellular and Molecular Life Sciences (CMLS)
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：71
- 期：23
- 页码：4653-4663
- 全文大小：1,664 KB
- 参考文献：1. Levin M (2007) Large-scale biophysics: ion flows and regeneration. Trends Cell Biol 17:261-70 CrossRef
2. Tai G, Reid B, Cao L, Zhao M (2009) Electrotaxis and wound healing: experimental methods to study electric fields as a directional signal for cell migration. Methods Mol Biol 571:77-7 CrossRef
3. Forrester JV, Lois N, Zhao M, McCaig C (2007) The spark of life: the role of electric fields in regulating cell behaviour using the eye as a model system. Ophthalmic Res 39:4-6 CrossRef
4. Funk RH, Monsees T, Ozkucur N (2009) Electromagnetic effects: from cell biology to medicine. Prog Histochem Cytochem 43:177-64 CrossRef
5. Ozkucur N, Epperlein HH, Funk RH?(2010) Ion imaging during axolotl tail regeneration in vivo. Dev Dyn 239:2048-057
6. Zhao M (2009) Electrical fields in wound healing: an overriding signal that directs cell migration. Semin Cell Dev Biol 20:674-82 CrossRef
7. Ozkucur N, Perike S, Sharma P, Funk RH (2011) Persistent directional cell migration requires ion transport proteins as direction sensors and membrane potential differences in order to maintain directedness. BMC Cell Biol 12:4 CrossRef
8. Ozkucur N, Monsees TK, Perike S, Do HQ et al (2009) Local calcium elevation and cell elongation initiate guided motility in electrically stimulated osteoblast-like cells. PLoS One 4:e6131 CrossRef
9. Schwab A, Wulf A, Schulz C, Kessler W et al (2006) Subcellular distribution of calcium-sensitive potassium channels (IK1) in migrating cells. J Cell Physiol 206:86-4 CrossRef
10. Djamgoz MBA, Mycielska M, Madeja Z, Fraser SP et al (2001) Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltage-gated Na+ channel activity. J Cell Sci 114:2697-705
11. Wei C, Wang X, Chen M, Ouyang K et al (2009) Calcium flickers steer cell migration. Nature 457:901-05 CrossRef
12. Perike S, Ozkucur N, Sharma P, Staroske W et al (2014) Phospho-NHE3 forms membrane patches and interacts with beta-actin to sense and maintain constant direction during cell migration. Exp Cell Res?324:13-9
13. Alexander RT, Malevanets A, Durkan AM, Kocinsky HS et al (2007) Membrane curvature alters the activation kinetics of the epithelial Na+/H+ exchanger, NHE3. J Biol Chem 282:7376-384 CrossRef
14. Bunnell TM, Burbach BJ, Shimizu Y, Ervasti JM (2011) Beta-actin specifically controls cell growth, migration, and the G-actin pool. Mol Biol Cell 22:4047-058 CrossRef
15. Alexander RT, Jaumouille V, Yeung T, Furuya W et al (2011) Membrane surface charge dictates the structure and function of the epithelial Na+/H+ exchanger. EMBO J 30:679-91 CrossRef
16. Vargas-Lopes C, Madeira C, Kahn SA, Albino do Couto I et al (2011) Protein kinase C activity regulates d -serine availability in the brain. J Neurochem 116:281-90
17. Reyland ME (2009) Protein kinase C isoforms: multi-functional regulators of cell life and death. Front Biosci 14:2386-399 CrossRef
18. Battaini F, Pascale A (2005) Protein kinase C signal transduction regulation in physiological and pathological aging. Ann N Y Acad Sci 1057:177-92- 作者单位：Nurdan ?zkucur (1) (2) (3)
Bing Song (2) (4)
Sharanya Bola (1)
Lei Zhang (2) (5)
Brian Reid (2)
Guo Fu (6)
Richard H. W. Funk (1) (7)
Min Zhao (2)
1. Department of Anatomy, Medical Theoretical Center, Technische Universit?t Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
2. Department of Dermatology and Department of Ophthalmology, Institute for Regenerative Cures, School of Medicine, University of California at Davis, Davis, CA, 95817, USA
3. Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA
4. School of Dentistry, Cardiff Institute of Tissue Engineering and Repair, Cardiff University, Cardiff, CF14 4XY, UK
5. Department of Occupational Health, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, China
6. The Scripps Research Institute, La Jolla, CA, 92037, USA
7. CRTD/DFG-Center for Regenerative Therapies Dresden-Cluster of Excellence, Tatzberg 47/49, 01307, Dresden, Germany- ISSN：1420-9071
- 作者单位：Nurdan ?zkucur (1) (2) (3)
文摘
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 PKCη isoform impairs directional cell migration in HEK 293 cells in the presence of a persistent directional cue (0.25-.3?V/mm of EF for 2?h). Further, we found that pNHE3 forms complexes with both PKCη and ?-tubulin, suggesting that these molecules may regulate the microtubule-organizing center. In addition, cellular pNHE3 content was reduced significantly when PKCη was inhibited during directional cell migration. Taken together, these data suggest that PKCη-dependent phosphorylation of NHE3 and the formation of pNHE3/PKCη/?-tubulin complexes at the leading edge of the cell are required for directional cell migration in an EF.