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
Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
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: urn:nbn:se:liu:diva-90024ISBN: 978-91-7519-690-9 (print)OAI: oai:DiVA.org:liu-90024DiVA: diva2:611254
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
List of papers
1. Aquaporin 9 phosphorylation mediates membrane localization and neutrophil polarization
Open this publication in new window or tab >>Aquaporin 9 phosphorylation mediates membrane localization and neutrophil polarization
Show others...
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
Keyword
AQP9, cell migration, Rac, water fluxes, osmosis, hydrostatic pressure
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-72257 (URN)10.1189/jlb.0910540 (DOI)000296716000014 ()
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
2. Fluxes of Water through Aquaporin 9 Weaken Membrane-Cytoskeleton Anchorage and Promote Formation of Membrane Protrusions
Open this publication in new window or tab >>Fluxes of Water through Aquaporin 9 Weaken Membrane-Cytoskeleton Anchorage and Promote Formation of Membrane Protrusions
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, e59901- p.Article in journal (Refereed) Published
Abstract [en]

All modes of cell migration require rapid rearrangements of cell shape, allowing the cell to navigate within narrow spaces in an extracellular matrix. Thus, a highly flexible membrane and a dynamic cytoskeleton are crucial for rapid cell migration. Cytoskeleton dynamics and tension also play instrumental roles in the formation of different specialized cell membrane protrusions, viz. lamellipodia, filopodia and membrane blebs. The flux of water through membrane-anchored water channels, known as aquaporins (AQPs) has recently been implicated in the regulation of cell motility, and here we provide novel evidence for the role of AQP9 in the development of various forms of membrane protrusion. Using multiple imaging techniques and cellular models we show that: (i) AQP9 induced and accumulated in filopodia, (ii) AQP9-associated filopodial extensions preceded actin polymerization, which was in turn crucial for their stability and dynamics, and (iii) minute, local reductions in osmolarity immediately initiated small dynamic bleb-like protrusions, the size of which correlated with the reduction in osmotic pressure. Based on this, we present a model for AQP9-induced membrane protrusion, where the interplay of water fluxes through AQP9 and actin dynamics regulate the cellular protrusive and motile activity of cells.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90022 (URN)10.1371/journal.pone.0059901 (DOI)000318840100033 ()
Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2017-12-06Bibliographically approved
3. Water fluxes through aquaporin-9 prime epithelial cells for rapid wound healing
Open this publication in new window or tab >>Water fluxes through aquaporin-9 prime epithelial cells for rapid wound healing
Show others...
2013 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 430, no 3, 993-998 p.Article in journal (Refereed) Published
Abstract [en]

Cells move along surfaces both as single cells and multi-cellular units. Recent research points toward pivotal roles for water flux through aquaporins (AQPs) in single cell migration. Their expression is known to facilitate this process by promoting rapid shape changes. However, little is known about the impact on migrating epithelial sheets during wound healing and epithelial renewal. Here, we investigate and compare the effects of AQP9 on single cell and epithelial sheet migration. To achieve this, MDCK-1 cells stably expressing AQP9 were subjected to migration assessment. We found that AQP9 facilitated cell locomotion at both the single and multi-cellular level. Furthermore, we identified major differences in the monolayer integrity and cell size upon expression of AQP9 during epithelial sheet migration, indicating a rapid volume-regulatory mechanism. We suggest a novel mechanism for epithelial wound healing based on AQP-induced swelling and expansion of the monolayer.

Place, publisher, year, edition, pages
Elsevier, 2013
Keyword
Cell migration, Aquaporins, AQP9, Wound healing, Cell motility
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-89749 (URN)10.1016/j.bbrc.2012.11.125 (DOI)000314376100021 ()
Note

Funding Agencies|Swedish Research Council for Medicine and Health|2007-34832009-66492010-3045|

Available from: 2013-03-05 Created: 2013-03-05 Last updated: 2017-12-06

Open Access in DiVA

Water Fluxes and Cell Migration: How Aquaporin 9 Controls Cell Shape and Motility(1799 kB)1031 downloads
File information
File name FULLTEXT01.pdfFile size 1799 kBChecksum SHA-512
de246ee444cf13e9a5535c2c26239ad47b8bfa844da8ff2f8615020e37f521b766364419e7abfbb80046efe1899bf0b6f4ef7db419e6dad662400d12cdbfb126
Type fulltextMimetype application/pdf
omslag(1740 kB)66 downloads
File information
File name COVER01.pdfFile size 1740 kBChecksum SHA-512
ed67b727dcf74930b27a9b16200f6cf88b917d78da373a9b0b351f064226b7a5d168e7e1aaed3d45893aee71d08e7f02866e94e9ca6d6527721bf24ae0c601f3
Type coverMimetype application/pdf

Authority records BETA

Karlsson, Thommie

Search in DiVA

By author/editor
Karlsson, Thommie
By organisation
Medical MicrobiologyFaculty of Health Sciences
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1031 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1379 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