Signaling and membrane dynamics during
phagocytosis: many roads lead to the phagos(R)ome is a review by Niedergang &
Chavrier and was published in
Current Opinion in Cell Biology 2004, 16: 422-428.
Phagocytosis is the mechanism used by specialized cells such as macrophages, dendritic cells
and neutrophils to internalise, degrade and eventually present peptides derived
from particular antigens.
After recognition of ligands
on the particle, macrophage sends out pseudopods which gradually engulf and surround particles. This interaction is receptor-mediated. The
tips of the pseudopods fuse creating a cup surrounding the
particle. The actin cup
forms within seconds and disassembled within one to five minutes.
The
production of polarized membrane structures such as pseudopods requires several
cellular cortical activities to control actin filament assembly and membrane
delivery in a coordinated manner. The signal pathway that takes place
after ligand binding to FC receptor (for example Immunoglobulin). It includes
multiple kinases and other compounds and phosphorylation of activation motif on
the receptor that acts as binding site for many enzymes and adaptors that are
required for phagocytosis.
Signal transduction leads to actin polymerization and actin filament accumulation underneath the plasma membrane,
which are thought to provide the driving force for membrane extension around
the particle. Control
of actin filament polymerization in the
phagocytotic cup depends on proteins including actin, ARF and Rho-family GTPases.
Myosin motors, for example Myosin-X, are also involved in the generation of contractility in the phagocytotic cup. The
contractility is necessary for particle engulfment and phagosome closure.
After
closure, the phagosome undergoes a series of fusion events with endocytic
compartments. During
maturation, phagosomes migrate on microtubules from the cell periphery to a
perinuclear location.
Hydrolases delivered to the phagosomal lumen by late endosomes and lysosomes contribute to the degradation of the ingested
material. Peptides derived from processing are then loaded on major histocompatibility complex class II molecules.
MHC
class II molecules are then expressed on the surface of the phagocytotic cell
to activate T lymphocytes. Phagocytotic antigens can also be presented by MHC class I molecules and activate cytotoxic T lymphocytes in a process called "cross-presentation".
This review focused on recent data concerning phagocytosis in macrophages and dendritic cells. The mechanism might
differ slightly in other professional phagocytes and in non-professional cells
ingesting apoptotic debris.