Aquaporin 9 phosphorylation mediates membrane localization and neutrophil polarization

Journal of Leukocyte Biology

Marco A. O. Magalhães ¹  Vesa-Matti Loitto²  Richard P. Ellen¹  Thommie Karlsson²  Karl-Eric Magnusson and²  Michael Glogauer¹ 

[1]  Matrix Dynamics Group and Dental Research Institute, University of Toronto, Faculty of Dentistry, Toronto, Ontario, Canada Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden;Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden;

关键词: AQP9;    cell migration;    Rac;    water fluxes;    osmosis;    hydrostatic pressure;   

DOI  :  10.1189/jlb.0910540

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Neutrophils are of prime importance in the host innate defense against invading microorganisms by using two primary mechanismslocomotion toward and phagocytosis of the prey. Recent research points to pivotal roles for water channels known as AQPs in cell motility. Here, we focused on the role of AQP9 in chemoattractant-induced polarization and migration of primary mouse neutrophils and neutrophil-like HL60 cells. We found that AQP9 is phosphorylated downstream of fMLFR or PMA stimulation in primary human neutrophils. The dynamics of AQP9 were assessed using GFP-tagged AQP9 constructs and other fluorescent markers through various live-cell imaging techniques. Expression of WT or the phosphomimic S11D AQP9 changed cell volume regulation as a response to hyperosmotic changes and enhanced neutrophil polarization and chemotaxis. WT AQP9 and S11D AQP9 displayed a very dynamic distribution at the cell membrane, whereas the phosphorylation-deficient S11A AQP9 failed to localize to the plasma membrane. Furthermore, we found that Rac1 regulated the translocation of AQP9 to the plasma membrane. Our results show that AQP9 plays an active role in neutrophil volume regulation and migration. The display of AQP9 at the plasma membrane depends on AQP9 phosphorylation, which appeared to be regulated through a Rac1-dependent pathway.

【 授权许可】

Unknown