Configuration of human dendritic cell cytoskeleton by Rho GTPases, the WAS protein, and differentiation

The cellular mechanisms that configure the cytoskeleton during migration of dendritic cells (DCs) are poorly understood. Immature DCs assemble specialized adhesion structures known as podosomes at their leading edge; these are associated with the localized recruitment of the Wiskott-Aldrich Syndrome...

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Bibliographic Details
Published in:Blood 2001-08, Vol.98 (4), p.1142-1149
Main Authors: Burns, Siobhan, Thrasher, Adrian J., Blundell, Michael P., Machesky, Laura, Jones, Gareth E.
Format: Article
Language:English
Subjects:
Actin-Related Protein 2
Actin-Related Protein 3
Actins - drug effects
Actins - metabolism
Actins - physiology
Biological and medical sciences
cdc42 GTP-Binding Protein - pharmacology
cdc42 GTP-Binding Protein - physiology
Cell Differentiation - physiology
Cell Movement - drug effects
Cytoskeletal Proteins
Cytoskeleton - drug effects
Cytoskeleton - enzymology
Dendritic Cells - cytology
Dendritic Cells - enzymology
Dendritic Cells - ultrastructure
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunopathology
Medical sciences
Proteins - pharmacology
Proteins - physiology
rac GTP-Binding Proteins - pharmacology
rac GTP-Binding Proteins - physiology
rho GTP-Binding Proteins - pharmacology
rho GTP-Binding Proteins - physiology
Wiskott-Aldrich Syndrome Protein
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Summary:The cellular mechanisms that configure the cytoskeleton during migration of dendritic cells (DCs) are poorly understood. Immature DCs assemble specialized adhesion structures known as podosomes at their leading edge; these are associated with the localized recruitment of the Wiskott-Aldrich Syndrome protein (WASp) and the actin organizing actin-related protein 2/3 complex. In immature DCs lacking WASp, podosomes are absent, residual dysmorphic lamellipodia and filopodia are nonpolarized, and migration is severely compromised. Microinjection studies indicate that podosome assembly and polarization require concerted action of Cdc42, Rac, and Rho, thereby providing a link between sequential protrusive and adhesive activity. Formation of podosomes is restricted to cells with an immature phenotype, indicating a specific role for these structures during the early migratory phase.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V98.4.1142