An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans

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In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms through the directed migration of its distal tip cells (DTCs), which are located at the tip of the growing gonad arms1. A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17 is synthesized and secreted from the muscle cells of the body wall, and diffuses to the gonad where it is required for DTC migration2. The mig-23 mutation causes defective migration of DTCs and interacts genetically with mig-17. Here, we report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase) required for glycosylation and proper localization of MIG-17. Our findings indicate that an NDPase affects organ morphogenesis through glycosylation of the MIG-17 ADAM protease.

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Figure 1: Wild-type and mutant gonad morphology.
Figure 2: Structure and activity of MIG-23.
Figure 3: Glycan modification of MIG-17.
Figure 4: Expression of mig-23 and mig-17.

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We thank A. Coulson, A. Fire, Y. Kohara, T. Stiernagle and the Caenorhabditis Genetics Center for materials; and M. Lamphier and A. Spence for critical reading of the manuscript. This work was supported by special grants for PRESTO (K. N.), CREST and Advanced Research on Cancer from the Ministry of Education, Culture and Science of Japan (K. M.).

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Correspondence to Kiyoji Nishiwaki.

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