liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Aquaporin 9 phosphorylation mediates membrane localization and neutrophil polarization
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
University of Toronto.
University of Toronto.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Show others and affiliations
2011 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 90, no 5, 963-973 p.Article in journal (Refereed) Published
Abstract [en]

Neutrophils are of prime importance in the host innate defense against invading microorganisms by using two primary mechanisms-locomotion 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.

Place, publisher, year, edition, pages
Society for Leukocyte Biology , 2011. Vol. 90, no 5, 963-973 p.
Keyword [en]
AQP9, cell migration, Rac, water fluxes, osmosis, hydrostatic pressure
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-72257DOI: 10.1189/jlb.0910540ISI: 000296716000014OAI: oai:DiVA.org:liu-72257DiVA: diva2:458811
Note
Funding Agencies|Swedish Research Council-Medicine|2006-74991007-34832010-3045|Swedish Research Council Natural Sciences|2009-6649|European Sciences Foundation (TraPPs-Euromembrane)||CIHR|MOP-86550|CIHR Group||Available from: 2011-11-24 Created: 2011-11-24 Last updated: 2017-12-08
In thesis
1. Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility
Open this publication in new window or tab >>Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Prerequisites for all modes of cell migration are cell-substratum interactions that require a sophisticated interplay of membrane dynamics and cytoskeletal rearrangement. Generally, a migrating cell is polarized with a distinct rear and front, from which it extends a wide and thin membrane protrusion- lamellipodium, small fingerlike projections- filopodia, and membrane blisters- blebs. The development of these structures is primarily driven by cytoskeletal contractions and actin polymerization, which are under regulation of several actin-binding proteins and the small GTPases Cdc42, Rac and Rho. Lamellipodia and filopodia are assumed to arise from polymerizing actin, pushing the membrane forward through a Brownian-ratchet mechanism. However, other models based on shifts in the local hydrostatic pressure have also been suggested since blebs are initially void of actin. Recently, fluxes of water through membrane-anchored water channels, aquaporins (AQPs), have been implicated in cell motility, while they appeared to localize to lamellipodia and facilitate cell locomotion. Indeed, expression of AQP9 was shown to induce filopodia in fibroblasts. Here, we have focused on the effects of AQP9 on cell morphology and motility. By using primarily live cell imaging of GFP-AQP9 and other cytoskeletal components we found that AQP9: (i) enhances cell polarization and migration in a Rac1 and serine11 phosphorylation-dependent manner in neutrophils, (ii) induces and accumulates in filopodia, before actin polymerization, (iii) locally deforms the membrane upon rapid reductions osmolarity, (iv) accumulates in the cell membrane underlying bleb development, (v) induces multiple protrusions and thereby impairs the intrinsic directionality, and (vi) facilitates epithelial wound closure through a mechanism involving swelling and expansion of the monolayer. Based on these findings, we have presented models for how water fluxes through AQPs aids actin polymerization in the formation of membrane protrusions. In summary, these models rely on localized accumulation of ion and water channels that control the influx of water and thereby the buildup of a hydrostatic pressure between the membrane and the cytoskeleton. Upon reaching a critical pressure, it will dislocate the membrane from the cytoskeleton and force it to protrude outwards. Moreover, this will promote a local cytoplasmic gel-to-sol transformation, which facilitates diffusion of cytoskeletal reactants. Hereby, we can furthermore assign to filopodia a role as osmo-sensors, protecting the cell from different osmotic loads. In addition, we have postulated a novel model for wound healing involving force generation by cell swelling. Taken together, this thesis provides the field of cell migration with solid evidence for pivotal roles of water fluxes through AQP9 in particular, but most likely AQPs in general, during cell locomotion and localized volume control.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 82 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1353
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90024 (URN)978-91-7519-690-9 (ISBN)
Public defence
2013-04-05, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2013-03-25Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Karlsson, ThommieLoitto, VesaMagnusson, Karl-Eric

Search in DiVA

By author/editor
Karlsson, ThommieLoitto, VesaMagnusson, Karl-Eric
By organisation
Department of Clinical and Experimental MedicineFaculty of Health SciencesMedical Microbiology
In the same journal
Journal of Leukocyte Biology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 175 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf