Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-12-6
pubmed:abstractText
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 p38(MAPK) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4205-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils.
pubmed:affiliation
Department of Experimental Hematology, Cincinnati Children's Hospital, 3333 BurnetAve, Cincinnati OH 45229, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't