title: Integrins Form an Expanding Diffusional Barrier that Coordinates Phagocytosis.
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.
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Spencer A
authors.initials: SA
authors.lastname: Freeman
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: Jesse
authors.initials: J
authors.lastname: Goyette
authors.affiliation: Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Furuya
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305-4401, USA.
authors.forename: Elliot C
authors.initials: EC
authors.lastname: Woods
authors.affiliation: Department of Chemistry and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305-4401, USA.
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Bertozzi
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, 120 Mason Farm Road, Chapel Hill, NC 27599-7260, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bergmeier
authors.affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON M5S 3E2, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Hinz
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
authors.forename: P Anton
authors.initials: PA
authors.lastname: van der Merwe
authors.affiliation: Department of Integrative Biology, University of Colorado, Denver, CO 80217-3364, USA.
authors.forename: Raibatak
authors.initials: R
authors.lastname: Das
authors.affiliation: 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.
authors.forename: Sergio
authors.initials: S
authors.lastname: Grinstein
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D010587:Phagocytosis; D000069261:Podosomes / Q000378:metabolism; D017434:Protein Structure, Tertiary; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D000199:Actins; D016023:Integrins; D017452:Receptors, IgG; D017493:Leukocyte Common Antigens; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3