August Krogh / CWS Seminar

Double seminar

14:00-15:00: Professor Sergio Grinstein seminar and discussion
15:00-16:00: Professor Amira Klip seminar and discussion
16:00-16:30: Reception and socializing

Tracking single molecules during phagocytosis: interplay of kinases and phosphatases

v/ Sergio Grinstein, Professor of biochemistry, University of Toronto, Canada

Abstract

Phagocytosis is initiated by lateral clustering of receptors, which in turn activates Src-family kinases (SFKs).  Activation of SFKs requires exclusion of tyrosine phosphatases from the area of particle engagement.  We investigated how the major phosphatase, CD45, is excluded from sites of contact with the target using single-molecule tracking.  A frustrated phagocytosis model was implemented to stabilize the focal plane. While individual CD45 molecules moved randomly in the plane of the membrane, they were displaced from the advancing phagocytic cup by an expanding diffusional barrier.  Micropatterning of IgG, the ligand of phagocytic receptors, was used to better define the relationship between engaged receptors and the progressive diffusional barrier.  Remarkably, the barrier extended well beyond the perimeter of the receptor-ligand engagement zone.

Second messengers generated by phagocytic receptor activation were found to activate integrins, which were shown to form the diffusion barrier that excluded CD45 by a kinetic segregation process akin to that described in the immunological synapse.  The expanding integrin wave facilitates the “zippering” of  receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagosome.

Relevant papers

Research profile

Dr. Sergio Grinstein completed his PhD in 1976 at the Centro de Investigacion y Estudios Avanzados, in Mexico City. He then spent two years as a post-doctoral fellow at the Hospital For Sick Children in Toronto, followed by a year in the Department of Biochemistry at the Federal Institute of Technology in Zurich. He is currently working at the Hospital For Sick Children in Toronto and has been Professor of Biochemistry at the University of Toronto since 1988. Dr. Grinstein is interested in the cell physiology and biophysics of innate immunity, particularly phagocytosis and host-pathogen interactions.

Time

19 November 2015

14:00-15:00: Professor Sergio Grinstein seminar and discussion
15:00-16:00: Professor Amira Klip seminar and discussion
16:00-16:30: Reception and socializing

Venue

Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen

Registration

Participation is free, but please register here.

For PhD students

PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar

Contact

Christian Frøsig, CFrosig@nexs.ku.dk, mobile +45 2875 1617

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