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Curvature recognition and force generation in phagocytosis


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 ofmyosin-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.

Author: Margaret ClarkeUlrike EngelJennifer GiorgioneAnnette Muller-
TaubenbergerJana PrasslerDouwe VeltmanGunther Gerisch
Credits/Source: BMC Biology 2010, 8:154