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Cell migration is a fundamental process required for
normal immune system function,embryonic
development,and tissue repair. Nevertheless,this
process also contributes to the pathogenesis of
several diseases,such as chronic inflammatory
disease and tumor cell invasion. The actin
cytoskeleton stands central in the process of cell
migration. CSF-1 is an important physiological
chemoattractant for macrophages. The mechanisms by
which CSF-1 affects actin cytoskeleton and induces
macrophage migration are not fully understood.In
particular,very little is known regarding the
role of WAVE2 protein in response to CSF-1. We have
identified for the first time WAVE2 as a pivotal
factor required for CSF-1-induced cell migration in
macrophages.We have also suggested a model for the
regulation of WAVE2 activity in vivo in which IRSp53
plays a central role in mediating the interaction
between Rac1 and WAVE2.Dissecting the fundamental
mechanisms underlying WAVE2-dependent CSF-1-induced
cell migration is important for understanding
macrophage-mediated diseases,like tumor metastasis,
and therefore holds the promise of newly effective
therapeutic approaches.
normal immune system function,embryonic
development,and tissue repair. Nevertheless,this
process also contributes to the pathogenesis of
several diseases,such as chronic inflammatory
disease and tumor cell invasion. The actin
cytoskeleton stands central in the process of cell
migration. CSF-1 is an important physiological
chemoattractant for macrophages. The mechanisms by
which CSF-1 affects actin cytoskeleton and induces
macrophage migration are not fully understood.In
particular,very little is known regarding the
role of WAVE2 protein in response to CSF-1. We have
identified for the first time WAVE2 as a pivotal
factor required for CSF-1-induced cell migration in
macrophages.We have also suggested a model for the
regulation of WAVE2 activity in vivo in which IRSp53
plays a central role in mediating the interaction
between Rac1 and WAVE2.Dissecting the fundamental
mechanisms underlying WAVE2-dependent CSF-1-induced
cell migration is important for understanding
macrophage-mediated diseases,like tumor metastasis,
and therefore holds the promise of newly effective
therapeutic approaches.