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 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. (Blood. 2001;98:1142-1149)
Burns
S
S
Molecular Immunology Unit, Institute of Child Health, University College London, United Kingdom.
Thrasher
A J
AJ
Blundell
M P
MP
Machesky
L
L
Jones
G E
GE
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000187:drug effects* / Q000201:enzymology; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology / Q000648:ultrastructure*; D006801:Humans; D011506:Proteins / Q000494:pharmacology* / Q000502:physiology; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein / Q000494:pharmacology / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000494:pharmacology / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000494:pharmacology* / Q000502:physiology
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; D003598:Cytoskeletal Proteins; D011506:Proteins; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins