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Cell. 2016 Jan 14;164(1-2):128-40. doi: 10.1016/j.cell.2015.11.048.

Integrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis.

Author information

1
Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
2
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
3
Department of Chemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305-4401, USA.
4
Department of Biochemistry and Biophysics, University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC 27599-7260, USA.
5
Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada.
6
Department of Integrative Biology, University of Colorado, Denver, CO 80217-3364, USA.
7
Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Keenan Research Centre, St. Michael's Hospital, Toronto, ON M5S 1T8, Canada. Electronic address: sergio.grinstein@sickkids.ca.

Abstract

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 Fcγ 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 Fcγ receptors, we found that the barrier extended well beyond the perimeter of the receptor-ligand engagement zone. Second messengers generated by Fcγ receptors activated integrins, which formed an actin-tethered diffusion barrier that excluded CD45. The expanding integrin wave facilitates the zippering of Fcγ receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagocytic cup.

PMID:
26771488
PMCID:
PMC4715264
DOI:
10.1016/j.cell.2015.11.048
[Indexed for MEDLINE]
Free PMC Article
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