Linked regulation of motility and integrin function in activated migrating neutrophils revealed by interference in remodelling of the cytoskeleton.

2.50
Hdl Handle:
http://hdl.handle.net/2436/20981
Title:
Linked regulation of motility and integrin function in activated migrating neutrophils revealed by interference in remodelling of the cytoskeleton.
Authors:
Anderson, Stephen I.; Behrendt, Barbara; Machesky, Laura M.; Insall, Robert H.; Nash, Gerard B.
Abstract:
Neutrophils migrate rapidly by co-ordinating regulation of their beta2-integrin adhesion with turnover of filamentous F-actin. The seven-protein Arp2/3 complex regulates actin polymerisation upon activation by proteins of the WASP-family. To investigate links between actin polymerisation, adhesion, and migration, we used a novel osmotic-shock method to load neutrophils with peptides: (1). WASP-WA and Scar-WA (which incorporate the actin- and Arp2/3-binding regions of WASP and Scar1), to compete with endogenous WASP-family members; (2). proline rich motifs (PRM) from the ActA protein of L. monocytogenes or from vinculin, which bind vasodilator-stimulated phosphoprotein (VASP), a regulator of cytoskeleton assembly. In a flow system, rolling-adherent neutrophils were stimulated with formyl tri-peptide. This caused rapid immobilisation, followed by migration with increasing velocity, supported by activated beta2-integrin CD11b/CD18. Loading ActA PRM (but not vinculin PRM) caused concentration-dependent reduction in migration velocity. At the highest concentration, unstimulated neutrophils had elevated F-actin and were rigid, but could not change their F-actin content or shape upon stimulation. Scar-WA also caused marked reduction in migration rate, but WASP-WA had a lesser effect. Scar-WA did not modify activation-dependent formation of F-actin or change in shape. However, a reduction in rate of downregulation of integrin adhesion appeared to contribute to impaired migration. These studies show that interference in cytoskeletal reorganisation that follows activation in neutrophils, can impair regulation of integrin function as well as motility. They also suggest a role of the Arp2/3 complex and WASP-family in co-ordinating actin polymerisation and integrin function in migrating neutrophils.
Citation:
Cell Motility and the Cytoskeleton, 54(2): 135-146
Publisher:
Wiley Interscience
Journal:
Cell Motility and the Cytoskeleton
Issue Date:
2003
URI:
http://hdl.handle.net/2436/20981
DOI:
10.1002/cm.10091
PubMed ID:
12529859
Additional Links:
http://www3.interscience.wiley.com/journal/102524780/abstract
Type:
Article
Language:
en
ISSN:
0886-1544
Appears in Collections:
Diabetes, Physiology and Molecular Medicine Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorAnderson, Stephen I.-
dc.contributor.authorBehrendt, Barbara-
dc.contributor.authorMachesky, Laura M.-
dc.contributor.authorInsall, Robert H.-
dc.contributor.authorNash, Gerard B.-
dc.date.accessioned2008-03-18T11:21:55Z-
dc.date.available2008-03-18T11:21:55Z-
dc.date.issued2003-
dc.identifier.citationCell Motility and the Cytoskeleton, 54(2): 135-146en
dc.identifier.issn0886-1544-
dc.identifier.pmid12529859-
dc.identifier.doi10.1002/cm.10091-
dc.identifier.urihttp://hdl.handle.net/2436/20981-
dc.description.abstractNeutrophils migrate rapidly by co-ordinating regulation of their beta2-integrin adhesion with turnover of filamentous F-actin. The seven-protein Arp2/3 complex regulates actin polymerisation upon activation by proteins of the WASP-family. To investigate links between actin polymerisation, adhesion, and migration, we used a novel osmotic-shock method to load neutrophils with peptides: (1). WASP-WA and Scar-WA (which incorporate the actin- and Arp2/3-binding regions of WASP and Scar1), to compete with endogenous WASP-family members; (2). proline rich motifs (PRM) from the ActA protein of L. monocytogenes or from vinculin, which bind vasodilator-stimulated phosphoprotein (VASP), a regulator of cytoskeleton assembly. In a flow system, rolling-adherent neutrophils were stimulated with formyl tri-peptide. This caused rapid immobilisation, followed by migration with increasing velocity, supported by activated beta2-integrin CD11b/CD18. Loading ActA PRM (but not vinculin PRM) caused concentration-dependent reduction in migration velocity. At the highest concentration, unstimulated neutrophils had elevated F-actin and were rigid, but could not change their F-actin content or shape upon stimulation. Scar-WA also caused marked reduction in migration rate, but WASP-WA had a lesser effect. Scar-WA did not modify activation-dependent formation of F-actin or change in shape. However, a reduction in rate of downregulation of integrin adhesion appeared to contribute to impaired migration. These studies show that interference in cytoskeletal reorganisation that follows activation in neutrophils, can impair regulation of integrin function as well as motility. They also suggest a role of the Arp2/3 complex and WASP-family in co-ordinating actin polymerisation and integrin function in migrating neutrophils.en
dc.language.isoenen
dc.publisherWiley Interscienceen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/102524780/abstracten
dc.subjectLeukocyte migrationen
dc.subjectCell Adhesionen
dc.subjectActin polymerisationen
dc.subjectPeptide loadingen
dc.subjectWASPen
dc.subjectArp2/3en
dc.subjectLeukocytes-
dc.subject.meshActin-Related Protein 2en
dc.subject.meshActin-Related Protein 3en
dc.subject.meshActinsen
dc.subject.meshAntigens, CD11ben
dc.subject.meshAntigens, CD18en
dc.subject.meshBacterial Proteinsen
dc.subject.meshCell Adhesionen
dc.subject.meshCell Adhesion Moleculesen
dc.subject.meshCell Movementen
dc.subject.meshCell Sizeen
dc.subject.meshCytoskeletal Proteinsen
dc.subject.meshCytoskeletonen
dc.subject.meshHumansen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMicrofilament Proteinsen
dc.subject.meshN-Formylmethionine Leucyl-Phenylalanineen
dc.subject.meshNeutrophilsen
dc.subject.meshOsmotic Pressureen
dc.subject.meshPeptide Fragmentsen
dc.subject.meshPhosphoproteinsen
dc.subject.meshPolymersen
dc.subject.meshProteinsen
dc.subject.meshVinculinen
dc.subject.meshWiskott-Aldrich Syndrome Proteinen
dc.subject.meshWiskott-Aldrich Syndrome Protein Familyen
dc.titleLinked regulation of motility and integrin function in activated migrating neutrophils revealed by interference in remodelling of the cytoskeleton.en
dc.typeArticleen
dc.identifier.journalCell Motility and the Cytoskeletonen

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