Biology Reference
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pathway may be independent of the PI3K pathway and involves the
chemoattractant-mediated SUMOylation of MEK1 and the downstream
MAP kinase ERK1. Together, these findings shed light on the mechanisms
regulating directional sensing and how these control the establishment of cell
polarity and chemotaxis.
Introduction
Chemotaxis, or directional cell movement up a chemical gradient, is a basic
property of eukaryotic cells, and is an essential component of a wide variety of
cellular processes, including inflammation, wound healing, embryogenesis and
morphogenesis, in diverse cell types such as neutrophils, macrophages and
Dictyostelium cells (Devreotes and Zigmond, 1988; Firtel and Chung, 2000;
Rickert et al., 2000). A chemoattractant gradient causes asymmetric
polymerization of filamentous actin (F-actin), leading to the protrusion of
the plasma membrane towards the highest concentration of chemoattractant
(leading edge), while myosin II-based contraction occurs in the posterior of
the cell body (uropod; Chung et al., 2001a). During these processes, cells move
up the gradient. It is impressive that cells are able to sense and respond to
gradients as shallow as 2%, which indicates there must be an asymmetric
distribution of intracellular components that amplifies the external
chemoattractant gradient. In Dictyostelium, as well as neutrophils, the
chemoattractant receptors and the coupled heterotrimeric G proteins are
uniformly localized along the cell surface or found in a very shallow gradient
that cannot account for the signal amplification (Xiao et al., 1997; Servant
et al., 1999; Jin et al., 2000; Janetopoulos et al., 2001). Recent studies that
employ GFP fusions of a variety of signalling proteins, combined with genetic
studies of genes required for directional sensing, have yielded new insights into
how chemotaxis is regulated. Here, we review our current understanding of
establishment of the internal signalling gradient in chemotaxis.
GPCR-mediated lipid signalling in chemotaxis of amoeboid
cells
Chemotaxis requires multiple, well-organized steps (Chung et al., 2001a;
Katanaev, 2001; Parent and Devreotes, 1999; Rickert et al., 2000): (1) binding
of the chemoattractant to cell-surface G protein-coupled receptors (GPCRs)
in the case of Dictyostelium cells and leukocytes; (2) amplifying an asymmetric
intracellular signal and the establishment of cell polarity; (3) the formation of
the leading edge and protrusion of the anterior part of cell (the leading edge is
rich in F-actin controlled by small GTPases of the Rho family); and (4)
