Abstract：
:Pregnancy-associated plasma protein A2 (PAPP-A2, also known as pappalysin-2) is a large metalloproteinase that is known to be required for normal postnatal growth and bone development in mice. We here report the detection of zebrafish papp-a2 mRNA in the chordamesoderm, notochord and lower jaw of zebrafish (Danio rerio) embryos, and that papp-a2-knockdown embryos display broadened axial mesoderm, notochord bends and severely reduced cranial cartilages. Genetic data link these phenotypes to insulin-like growth factor (Igf)-binding protein-3 (Igfbp-3) and bone morphogenetic protein (Bmp) signaling, and biochemical analysis show specific Igfbp-3 proteolysis by Papp-a2, implicating Papp-a2 in the modulation of Bmp signaling by Igfbp-3 proteolysis. Knockdown of papp-a2 additionally resulted in angiogenesis defects, strikingly similar to previous observations in embryos with mutations in components of the Notch system. Accordingly, we find that Notch signaling is modulated by Papp-a2 in vivo, and, furthermore, that human PAPP-A2 is capable of modulating Notch signaling independently of its proteolytic activity in cell culture. Based on these results, we conclude that Papp-a2 modulates Bmp and Notch signaling by independent mechanisms in zebrafish embryos. In conclusion, these data link pappalysin function in zebrafish to two different signaling pathways outside the IGF system.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Kjaer-Sorensen K,Engholm DH,Jepsen MR,Morch MG,Weyer K,Hefting LL,Skov LL,Laursen LS,Oxvig Cdoi
10.1242/jcs.152587subject
Has Abstractpub_date
2014-12-01 00:00:00pages
5027-37issue
Pt 23eissn
0021-9533issn
1477-9137pii
jcs.152587journal_volume
127pub_type
杂志文章abstract：:The specific phosphatase inhibitor okadaic acid (OA) induced fragmentation of the Golgi apparatus in interphase HeLa cells. Immunoelectron microscopy for galactosyltransferase identified a major Golgi fragment composed of a cluster of vesicles and tubules that was morphologically indistinguishable from the 'Golgi clus...
journal_title：Journal of cell science
pub_type： 杂志文章
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abstract：:Filamin (actin-binding protein) is a cytoskeletal protein that crosslinks actin filaments in vitro. Filamin is thought to be involved in a variety of cell types in stabilizing actin networks, and in platelets it may play a role in linking actin to the membrane. In this report, we describe a monoclonal antibody (Mab 6E...
journal_title：Journal of cell science
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1992-04-01 00:00:00
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更新日期：2012-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1242/jcs.021303
更新日期：2008-03-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-12-01 00:00:00
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journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
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更新日期：2004-01-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
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doi：
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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doi：
更新日期：1985-08-01 00:00:00
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：1997-09-01 00:00:00
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