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Fluxes of Water through Aquaporin 9 Weaken Membrane-Cytoskeleton Anchorage and Promote Formation of Membrane Protrusions
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Faculty of Dentistry, University of Toronto, Toronto, Canada.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
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2013 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 4, p. e59901-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.

Place, publisher, year, edition, pages
2013. Vol. 8, no 4, p. e59901-
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-90022DOI: 10.1371/journal.pone.0059901ISI: 000318840100033OAI: oai:DiVA.org:liu-90022DiVA, id: diva2:611252
Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2021-06-14Bibliographically approved
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. p. 82
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)
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Available from: 2013-03-15 Created: 2013-03-15 Last updated: 2023-02-07Bibliographically approved

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Karlsson, ThommieBolshakova, AnastasiaLoitto, VesaMagnusson, Karl-Eric

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