Fluxes of Water Through Aquaporin 9 Weaken Membrane-Cytoskeleton Anchorage and Promote Formation of Membrane Protrusions

PLoS One. 2013;8(4):e59901. doi: 10.1371/journal.pone.0059901. Epub 2013 Apr 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Aquaporins / metabolism*
  • Cytoskeleton / metabolism*
  • HEK293 Cells
  • Humans
  • Microscopy, Fluorescence
  • Myosins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Osmotic Pressure
  • Protein Multimerization
  • Protein Transport
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure
  • Time-Lapse Imaging
  • Tubulin / metabolism
  • Water / metabolism*

Substances

  • AQP9 protein, human
  • Actins
  • Aquaporins
  • BAIAP2 protein, human
  • MYO10 protein, human
  • Nerve Tissue Proteins
  • Tubulin
  • Water
  • Myosins

Grant support

This research was supported by the Swedish Research Council (Grant Nos 2007–3483, 2009–6649 and 2010–3045, www.vr.se). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.