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Published on: April 29, 2016
Prodomain-dependent tissue targeting of an ADAMTS protease controls cell migration in Caenorhabditis elegans
Shinji Ihara1, Kiyoji Nishiwaki
1RIKEN Center for Developmental Biology, Kobe, Japan.
Abstract:
Members of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted proteins play important roles in animal development and pathogenesis. However, the lack of in vivo models has hampered elucidation of the mechanisms by which these enzymes are recruited to specific target tissues and the timing of their activation during development. Using transgenic worms and primary cell cultures, here we show that MIG-17, an ADAMTS family protein required for gonadal leader cell migration in Caenorhabditis elegans, is recruited to the gonadal basement membrane in a prodomain-dependent manner. The activation of MIG-17 to control leader cell migration requires prodomain removal, which is suggested to occur autocatalytically in vitro. Although the prodomains of ADAMTS proteases have been implicated in maintaining enzymatic latency, polypeptide folding and secretion, our findings demonstrate that the prodomain has an unexpected function in tissue-specific targeting of MIG-17; this prodomain targeting function may be shared by other ADAMTSs including those in vertebrates.
Insights
The ADAMTS protein MIG-17 uses its prodomain for tissue targeting during development. Prodomain removal is essential for MIG-17 activation and gonadal leader cell migration in C. elegans.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Biology
Background:
- ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) proteins are crucial in development and disease.
- Understanding their tissue recruitment and activation mechanisms is limited by a lack of in vivo models.
Purpose of the Study:
- To investigate the mechanisms of tissue-specific recruitment and activation of the ADAMTS protein MIG-17.
- To elucidate the role of the MIG-17 prodomain in these processes.
Main Methods:
- Utilized transgenic Caenorhabditis elegans (worm) models.
- Employed primary cell cultures.
- Investigated prodomain-dependent recruitment and activation pathways.
Main Results:
- MIG-17 is recruited to the gonadal basement membrane via a prodomain-dependent mechanism.
- Prodomain removal is necessary for MIG-17 activation and subsequent leader cell migration.
- Autocatalytic activation of MIG-17 in vitro was observed.
Conclusions:
- The prodomain of MIG-17 plays a critical, previously unrecognized role in tissue-specific targeting.
- This prodomain-mediated targeting function may be conserved across species, including vertebrates.
- Findings provide insights into ADAMTS protein regulation during development.
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