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Article: Dendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14

TitleDendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14
Authors
KeywordsElectron microscopy
Podosome
Quantification
Issue Date2010
PublisherThe Company of Biologists Ltd.
Citation
Journal Of Cell Science, 2010, v. 123 n. 9, p. 1427-1437 How to Cite?
AbstractPodosomes are spot-like actin-rich structures formed at the ventral surface of monocytic and haematopoietic cells. Podosomes degrade extracellular matrix and are proposed to be involved in cell migration. A key question is whether podosomes form protrusions similar to the invadopodia of cancer cells. We characterised podosomes of immature dendritic cells using electron microscopy combined with both conventional and novel high-resolution structured illumination light microscopy. Dendritic cell podosomes are composed of actin foci surrounded by a specialised ring region that is rich in material containing paxillin. We found that podosomes were preferential sites for protrusion into polycarbonate filters impregnated with crosslinked gelatin, degrading up to 2 mm of matrix in 24 hours. Podosome-associated uptake of colloidal gold-labelled gelatin matrix appeared to occur via large phagosome-like structures or narrow tubular invaginations. The motor protein myosin-II was excluded from ring or core regions but was concentrated around them and the myosin-II inhibitor Blebbistatin reduced the length of podosome protrusions. Finally, we found that degradation, protrusion and endocytosis in this system are dependent on the matrix metalloproteinase MMP-14. We propose that podosomes mediate migration of dendritic cells through tissues by means of myosin-II-dependent protrusion coupled to MMP-14-dependent degradation and endocytosis.
Persistent Identifierhttp://hdl.handle.net/10722/129095
ISSN
2015 Impact Factor: 4.706
2015 SCImago Journal Rankings: 3.501
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
MRC
Hong Kong Research Grant CouncilGRF HKU 781808M
Funding Information:

We thank John James (University of Dundee, UK) for EM advice, Michele West (University of Dundee, UK) for discussions and Andreas Elkeries (DITABIS, Pforzheim, Germany) for technical advice. Giuilo Gabbiani, David J. Kwiatkowski and Robert Wallin (Karolinska Institutet, Stockholm, Sweden) kindly provided gelsolin-knockout cells. This research was funded by the MRC capacity studentship grant, MRC programme grant MRC (to C. W.), Hong Kong Research Grant Council GRF HKU 781808M (to Z. Z.). Deposited in PMC for release after 6 months.

References

 

DC FieldValueLanguage
dc.contributor.authorGawdenBone, Cen_HK
dc.contributor.authorZhou, Zen_HK
dc.contributor.authorKing, Een_HK
dc.contributor.authorPrescott, Aen_HK
dc.contributor.authorWatts, Cen_HK
dc.contributor.authorLucocq, Jen_HK
dc.date.accessioned2010-12-23T08:32:26Z-
dc.date.available2010-12-23T08:32:26Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Cell Science, 2010, v. 123 n. 9, p. 1427-1437en_HK
dc.identifier.issn0021-9533en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129095-
dc.description.abstractPodosomes are spot-like actin-rich structures formed at the ventral surface of monocytic and haematopoietic cells. Podosomes degrade extracellular matrix and are proposed to be involved in cell migration. A key question is whether podosomes form protrusions similar to the invadopodia of cancer cells. We characterised podosomes of immature dendritic cells using electron microscopy combined with both conventional and novel high-resolution structured illumination light microscopy. Dendritic cell podosomes are composed of actin foci surrounded by a specialised ring region that is rich in material containing paxillin. We found that podosomes were preferential sites for protrusion into polycarbonate filters impregnated with crosslinked gelatin, degrading up to 2 mm of matrix in 24 hours. Podosome-associated uptake of colloidal gold-labelled gelatin matrix appeared to occur via large phagosome-like structures or narrow tubular invaginations. The motor protein myosin-II was excluded from ring or core regions but was concentrated around them and the myosin-II inhibitor Blebbistatin reduced the length of podosome protrusions. Finally, we found that degradation, protrusion and endocytosis in this system are dependent on the matrix metalloproteinase MMP-14. We propose that podosomes mediate migration of dendritic cells through tissues by means of myosin-II-dependent protrusion coupled to MMP-14-dependent degradation and endocytosis.en_HK
dc.languageengen_US
dc.publisherThe Company of Biologists Ltd.-
dc.relation.ispartofJournal of Cell Scienceen_HK
dc.subjectElectron microscopyen_HK
dc.subjectPodosomeen_HK
dc.subjectQuantificationen_HK
dc.subject.meshAnimals-
dc.subject.meshCell Surface Extensions - drug effects - enzymology - ultrastructure-
dc.subject.meshDendritic Cells - drug effects - enzymology - ultrastructure-
dc.subject.meshExtracellular Matrix - drug effects - enzymology - ultrastructure-
dc.subject.meshMatrix Metalloproteinase 14 - deficiency - metabolism-
dc.titleDendritic cell podosomes are protrusive and invade the extracellular matrix using metalloproteinase MMP-14en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9533&volume=123&issue=9&spage=1427&epage=1437&date=2010&atitle=Dendritic+cell+podosomes+are+protrusive+and+invade+the+extracellular+matrix+using+metalloproteinase+MMP-14-
dc.identifier.emailZhou, Z:zhongjun@hkucc.hku.hken_HK
dc.identifier.authorityZhou, Z=rp00503en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1242/jcs.056515en_HK
dc.identifier.pmid20356925-
dc.identifier.pmcidPMC2858019-
dc.identifier.scopuseid_2-s2.0-77951719523en_HK
dc.identifier.hkuros178654en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77951719523&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume123en_HK
dc.identifier.issue9en_HK
dc.identifier.spage1427en_HK
dc.identifier.epage1437en_HK
dc.identifier.isiWOS:000276912300007-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGawdenBone, C=33767621400en_HK
dc.identifier.scopusauthoridZhou, Z=8631856300en_HK
dc.identifier.scopusauthoridKing, E=16316347700en_HK
dc.identifier.scopusauthoridPrescott, A=7005983965en_HK
dc.identifier.scopusauthoridWatts, C=7202527327en_HK
dc.identifier.scopusauthoridLucocq, J=7004937006en_HK
dc.identifier.citeulike6945117-

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