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Publication : Integrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis.

First Author  Freeman SA Year  2016
Journal  Cell Volume  164
Issue  1-2 Pages  128-140
PubMed ID  26771488 Mgi Jnum  J:230666
Mgi Id  MGI:5763519 Doi  10.1016/j.cell.2015.11.048
Citation  Freeman SA, et al. (2016) Integrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis. Cell 164(1-2):128-40
abstractText  Phagocytosis is initiated by lateral clustering of receptors, which in turn activates Src-family kinases (SFKs). Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. The mobility of CD45 increased markedly upon engagement of Fcgamma receptors. While individual CD45 molecules moved randomly, they were displaced from the advancing phagocytic cup by an expanding diffusional barrier. By micropatterning IgG, the ligand of Fcgamma receptors, we found that the barrier extended well beyond the perimeter of the receptor-ligand engagement zone. Second messengers generated by Fcgamma receptors activated integrins, which formed an actin-tethered diffusion barrier that excluded CD45. The expanding integrin wave facilitates the zippering of Fcgamma receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagocytic cup.
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