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Open Access Highly Accessed Research article

Curvature recognition and force generation in phagocytosis

Margaret Clarke1, Ulrike Engel2, Jennifer Giorgione1, Annette Müller-Taubenberger3, Jana Prassler4, Douwe Veltman5 and Günther Gerisch4*

Author affiliations

1 Program in Genetic Models of Disease, Oklahoma Medical Research Foundation, Oklahoma City, OK 73121, USA

2 Nikon Imaging Center at the University of Heidelberg, Bioquant, 69120 Heidelberg, Germany

3 Institut für Zellbiologie, Ludwig-Maximilians-Universität München, 80336 München, Germany

4 Max-Planck-Institut für Biochemie, 82152 Martinsried, Germany

5 Beatson Institute for Cancer Research, Glasgow G61 1BD, UK

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Citation and License

BMC Biology 2010, 8:154  doi:10.1186/1741-7007-8-154

Published: 29 December 2010

Abstract

Background

The uptake of particles by actin-powered invagination of the plasma membrane is common to protozoa and to phagocytes involved in the immune response of higher organisms. The question addressed here is how a phagocyte may use geometric cues to optimize force generation for the uptake of a particle. We survey mechanisms that enable a phagocyte to remodel actin organization in response to particles of complex shape.

Results

Using particles that consist of two lobes separated by a neck, we found that Dictyostelium cells transmit signals concerning the curvature of a surface to the actin system underlying the plasma membrane. Force applied to a concave region can divide a particle in two, allowing engulfment of the portion first encountered. The phagosome membrane that is bent around the concave region is marked by a protein containing an inverse Bin-Amphiphysin-Rvs (I-BAR) domain in combination with an Src homology (SH3) domain, similar to mammalian insulin receptor tyrosine kinase substrate p53. Regulatory proteins enable the phagocyte to switch activities within seconds in response to particle shape. Ras, an inducer of actin polymerization, is activated along the cup surface. Coronin, which limits the lifetime of actin structures, is reversibly recruited to the cup, reflecting a program of actin depolymerization. The various forms of myosin-I are candidate motor proteins for force generation in particle uptake, whereas myosin-II is engaged only in retracting a phagocytic cup after a switch to particle release. Thus, the constriction of a phagocytic cup differs from the contraction of a cleavage furrow in mitosis.

Conclusions

Phagocytes scan a particle surface for convex and concave regions. By modulating the spatiotemporal pattern of actin organization, they are capable of switching between different modes of interaction with a particle, either arresting at a concave region and applying force in an attempt to sever the particle there, or extending the cup along the particle surface to identify the very end of the object to be ingested. Our data illustrate the flexibility of regulatory mechanisms that are at the phagocyte's disposal in exploring an environment of irregular geometry.