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SUMMARY:Imaging phatocytosis: receptors\, phospholipids and the cytoskelet
 on    Host: Rob Kay (MRC-LMB) - Professor Sergio Grinstein - University of
  Toronto
DTSTART:20150423T150000Z
DTEND:20150423T160000Z
UID:TALK58559@talks.cam.ac.uk
CONTACT:Susan
DESCRIPTION:Phagocytosis is initiated by lateral clustering of receptors\,
  which in turn activates Src-family kinases (SFKs).  Activation of SFKs re
 quires exclusion of tyrosine phosphatases from the area of particle engage
 ment.  We investigated how the major phosphatase\, CD45\, is excluded from
  sites of contact with the target using single-molecule tracking.  A frust
 rated phagocytosis model was implemented to stabilize the focal plane. The
  mobility of CD45\, which was largely confined in unstimulated macrophages
 \, increased markedly upon engagement of phagocytic (Fcγ) receptors.  Whi
 le individual CD45 molecules moved randomly in the plane of the membrane\,
  they were displaced from the advancing phagocytic cup by an expanding dif
 fusional barrier.  Micropatterning of IgG\, the ligand of Fcγ receptors\,
  was used to better define the relationship between engaged receptors and 
 the progressive diffusional barrier.  Remarkably\, the barrier extended we
 ll beyond the perimeter of the receptor-ligand engagement zone.  Second me
 ssengers generated by Fcγ receptor activation were found to activate inte
 grins\, which were shown to form the diffusion barrier that excluded CD45 
 by a kinetic segregation process akin to that described in the immunologic
 al synapse.  The expanding integrin wave facilitates the “zippering” o
 f Fcγ receptors onto the target and integrates the information from spars
 e receptor-ligand complexes\, coordinating the progression and ultimate cl
 osure of the phagocytic cup.                          
LOCATION:The Max Perutz Lecture Theatre\, MRC-LMB\, Francis Crick Avenue\,
  Cambridge CB2 0QH
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