tailieunhanh - Báo cáo khoa học: Stage-specific activation of MIG-17⁄ADAMTS controls cell migration in Caenorhabditis elegans

The activation of ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family proteases depends on removal of the prodomain. Although several studies suggest that ADAMTS activities play roles in development, homeostasis and disease, it remains unclear when and where the enzymes are activated in vivo. | ễFEBS Journal Stage-specific activation of MIG-17 ADAMTS controls cell migration in Caenorhabditis elegans Shinji Ihara1 and Kiyoji Nishiwaki1 2 1 RIKEN Center for DevelopmentalBiology Hyogo Japan 2 Department of Bioscience Kwansei-Gakuin University Hyogo Japan Keywords activation ADAMTS protease antibody Caenorhabditis elegans MIG-17 Correspondence K. Nishiwaki Department of Bioscience Kwansei-Gakuin University 2-1 Gakuen Sanda Hyogo 669-1337 Japan Fax 81 79 565 9077 Tel 81 79 565 7639 E-mail nishiwaki@ Received 18 April2008 revised 9 June 2008 accepted 25 June 2008 doi The activation of ADAMTS a disintegrin and metalloprotease with thrombospondin motifs family proteases depends on removal of the prodomain. Although several studies suggest that ADAMTS activities play roles in development homeostasis and disease it remains unclear when and where the enzymes are activated in vivo. MIG-17 a Caenorhabditis elegans glycoprotein belonging to the ADAMTS family is secreted from the body wall muscle cells and localizes to the gonadal basement membrane to control the migration of gonadal distal tip cells. Here we developed a monoclonal antibody that recognizes the N-terminal neo-epitope of the activated MIG-17. In western blotting the antibody specifically detected the activated form the signal for which dramatically increased during the third and fourth larval stages when MIG-17 is required to direct distal tip cell migration. In in situ staining the monoclonal antibody recognized the activated form in the basement membrane whereas it failed to detect a processing-resistant mutant form localized to the basement membrane. MIG-17 was activated in the basement membranes of the muscle intestine and gonad in the third larval stage and downregulated in nongonadal basement membranes in young adults and in gonadal basement membranes in older adults. Thus the activation of MIG-17 is regulated in a spatiotemporal manner during C. elegans