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To cleave or not to cleave: the proteolytic and non‐proteolytic functions of ADAMs in neural crest induction (609.11)
Author(s) -
Li Jie Jing,
Perfetto Mark,
Wei Shuo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.609.11
Subject(s) - neural crest , disintegrin , microbiology and biotechnology , wnt signaling pathway , proteases , proteolytic enzymes , biology , gene knockdown , protease , cathepsin , metalloproteinase , gene , signal transduction , genetics , matrix metalloproteinase , biochemistry , embryo , enzyme
The induction and subsequent development of the neural crest require highly coordinated interactions among genes and pathways. The disintegrin metalloproteinase (ADAM) family proteases have emerged as key regulators of gene and pathway interactions, mainly through their functions as proteolytic “molecular scissors”. Here we show that both the proteolytic and non‐proteolytic activities of ADAMs are important for neural crest induction. Knockdown of either ADAM13 or ADAM19 inhibits the induction of cranial neural crest (CNC) in Xenopus tropicalis . ADAM13 functions as a major regulator of canonical Wnt signaling, a signaling pathway that is essential for CNC induction. This is achieved through ADAM13‐mediated cleavage of class B ephrins, which we identified as new Wnt antagonists. By contrast, the proteolytic activity of ADAM19 seems to be dispensable for its function in CNC induction. Surprisingly, we found that ADAM19 directs CNC induction by binding and stabilizing ADAM13. These results highlight the importance of protease‐protease interaction as part of the gene interaction network in neural crest development. Grant Funding Source : Supported by the NIH