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.
Highlights
Cell migration requires tightly regulated membrane dynamics and cytoskeleton remodeling to allow for rapid shape change and navigation through the extracellular matrix (ECM) of different tissues
TagRFP-AQP9 localized to the plasma membrane and induced a filopodial phenotype as evident from control transfections with an empty tagRFP vector and a GFP-membrane vector (GFP-Mem; Fig. 1A)
This was further confirmed by quantification of peripheral filopodia/mm perimeter (P,0.0005, Students T-test, n = 34–43 cells, Fig. 1B) where GFP-AQP9- and GFP-Mem-transfected cells displayed a mean of 0.16 (60.01) and 0.10 (60.01) filopodia/mm respectively
Summary
Cell migration requires tightly regulated membrane dynamics and cytoskeleton remodeling to allow for rapid shape change and navigation through the extracellular matrix (ECM) of different tissues. Plasma membrane-associated formins nucleate actin filaments, which can explain the appearance of filopodia upon knock-down of the Arp2/3 complex and other lamellipodium-associated proteins [32]. Still, it is debated which of the models being most relevant [31,32,33]. The tension of the cortical actin cytoskeleton has been assumed to increase the local pressure and initiate a bleb, which in turn may neutralize the pressure by allowing fluid to flow freely into the bleb from the poro-elastic, gellike cytoplasm [42,43] Such bleb-based motile behavior has been observed for cells migrating in 3D matrices [6,11,44]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
