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SUMMARY:Cytoskeletal Control of Leukocyte Chemotaxis - Michael Sixt\, IST 
 Austria
DTSTART:20130513T151500Z
DTEND:20130513T170000Z
UID:TALK43665@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The organizational principle of the immune system is based on 
 high-speed cell motility. Accordingly\, immune cells migrate up to 100 tim
 es faster than mesenchymal or epithelial cell types. Although the biophysi
 cal migration mode of such fast cells is still poorly investigated some pr
 inciples are emerging and it is now well established that leukocytes do no
 t strictly rely on transmembrane adhesion receptors when they crawl throug
 h the interstitial environment\, which is usually a 3D scaffold of extrace
 llular matrix molecules. Instead\, leukocytes are able to directly transdu
 ce force by deformations of the cell body. Using in vitro and ex vivo imag
 ing approaches we demonstrate that deformation based migration is not the 
 default strategy of leukocyte locomotion but rather part of a plasticity p
 rogram that allows the cells to instantaneously switch between adhesion re
 ceptor dependent and independent migration. We find that invasion of dense
  matrices and crawling over stiff surfaces relies on adhesion\, while migr
 ation in the confined space of an interstitium does not and that leukocyte
 s can shift back and forth between these modes without altering their prot
 eome. We find that apart from the geometry of the extracellular environmen
 t also the distribution of the guidance cue can dictate the locomotion str
 ategy as immobilized cues preferentially cause adhesive migration whereas 
 soluble cues trigger adhesion-independent movement. \nThe force-generating
  module of leukocytes is exclusively based on actomyosin protrusions and c
 ontractions. But also here the cells show enormous plasticity and we found
  that blocking contractility shifts the cells towards an entirely protrusi
 ve locomotion strategy\, while dampening protrusion activates the blebbing
  mode. When interfering with actin nucleators we found that ablation of Ar
 p2/3 activity at the leading edge abrogated branching and transformed the 
 cells from roundish/amoeboid to an almost linear elongated cell shape. How
 ever\, this did not slow down locomotion\, but merely prevented the cells 
 from turning and responding to directional cues\, while actual speed was e
 ven accelerated. \n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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