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Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils
- Source :
- Blood. 108:4205-4213
- Publication Year :
- 2006
- Publisher :
- American Society of Hematology, 2006.
-
Abstract
- Neutrophil transmigration into tissue is a multiple-step process that results from a coordinated rearrangement of the cytoskeleton and adhesion complexes. Assembly and disassembly of actin and adhesion structures dictate motility behavior, while polarity and gradient sensing provide directionality to the cell movement. Here, using mice deficient in the CDC42 regulator CDC42 GTPase-activating protein (CDC42GAP), we demonstrate that CDC42 activity separately regulates neutrophil motility and directionality. CDC42GAP–/– neutrophils showed increased motility, while directed migration was defective. Podosome-like structures present at the leading edge in wild-type neutrophils were significantly reduced in CDC42GAP–/– cells. CDC42GAP–/– neutrophils also showed increased lateral and tail filopodia-like formation, and excess membrane protrusions. We further suggest that CDC42GAP-mediated extracellular signal–regulated kinase (ERK) activity regulates motility associated with podosome-like structures at the cell leading edge, while CDC42GAP-induced p38MAPK phosphorylation regulates directed migration by antagonizing filopodia assembly. Overall, this study reveals that CDC42 activity regulates both motility and directionality in neutrophils, but via distinct mitogen-activated protein kinase (MAPK) pathways.
- Subjects :
- Mice, Knockout
MAPK/ERK pathway
Podosome
MAP Kinase Signaling System
Neutrophils
Immunology
Cell leading edge
Motility
macromolecular substances
Cell Biology
Hematology
CDC42
Biology
Biochemistry
Cell biology
Mice
Cell Movement
Animals
Pseudopodia
Mitogen-Activated Protein Kinases
cdc42 GTP-Binding Protein
Protein kinase A
Cytoskeleton
Filopodia
Cells, Cultured
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....39fb337aed792431338e7880c1adc9f5