| ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. | |
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MedLine Citation:
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PMID: 19922873 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We show that combinatorial mouse alleles for the secreted metalloproteases Adamts5, Adamts20 (bt), and Adamts9 result in fully penetrant soft-tissue syndactyly. Interdigital webs in Adamts5(-/-);bt/bt mice had reduced apoptosis and decreased cleavage of the proteoglycan versican; however, the BMP-FGF axis, which regulates interdigital apoptosis was unaffected. BMP4 induced apoptosis, but without concomitant versican proteolysis. Haploinsufficiency of either Vcan or Fbln1, a cofactor for versican processing by ADAMTS5, led to highly penetrant syndactyly in bt mice, suggesting that cleaved versican was essential for web regression. The local application of an aminoterminal versican fragment corresponding to ADAMTS-processed versican, induced cell death in Adamts5(-/-);bt/bt webs. Thus, ADAMTS proteases cooperatively maintain versican proteolysis above a required threshold to create a permissive environment for apoptosis. The data highlight the developmental significance of proteolytic action on the ECM, not only as a clearance mechanism, but also as a means to generate bioactive versican fragments. |
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Authors:
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Daniel R McCulloch; Courtney M Nelson; Laura J Dixon; Debra L Silver; James D Wylie; Volkhard Lindner; Takako Sasaki; Marion A Cooley; W Scott Argraves; Suneel S Apte |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Developmental cell Volume: 17 ISSN: 1878-1551 ISO Abbreviation: Dev. Cell Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-11-20 Completed Date: 2009-12-14 Revised Date: 2011-07-08 |
Medline Journal Info:
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Nlm Unique ID: 101120028 Medline TA: Dev Cell Country: United States |
Other Details:
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Languages: eng Pagination: 687-98 Citation Subset: IM |
Affiliation:
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Department of Biomedical Engineering, Lerner Research Institute, ND20-Cleveland Clinic, Cleveland, OH 44195, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
/
deficiency,
genetics,
metabolism* Animals Apoptosis Body Patterning Calcium-Binding Proteins / metabolism Extremities / embryology* Gene Expression Regulation, Developmental* Gene Expression Regulation, Enzymologic Mice Mice, Knockout Versicans / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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AR050953/AR/NIAMS NIH HHS; AR49930/AR/NIAMS NIH HHS; AR53890/AR/NIAMS NIH HHS; HL095067/HL/NHLBI NIH HHS; R01 AR049930-02/AR/NIAMS NIH HHS; R01 AR049930-03/AR/NIAMS NIH HHS; R01 AR049930-04/AR/NIAMS NIH HHS; R01 AR049930-05/AR/NIAMS NIH HHS; R01 AR053890-02/AR/NIAMS NIH HHS; R01 HL095067-03/HL/NHLBI NIH HHS; R56 AR049930-06A2/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium-Binding Proteins; 0/fibulin; 126968-45-4/Versicans; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/Adamts20 protein, mouse; EC 3.4.24.-/Adamts5 protein, mouse; EC 3.4.24.-/Adamts9 protein, mouse |
| Comments/Corrections | |
Comment In:
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Dev Cell. 2009 Nov;17(5):584-6
[PMID:
19922863
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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