New roles for protein modifications in cell migration

In every stage of development, cells are directed to make their way through the body to contribute to the building of or take up residence in new tissues and organs. The guidance of cell migration is achieved by signals intrinsic to the cell or from its surrounding environment. In work published on December 21 in the online edition of Nature Cell Biology, the RIKEN Center for Developmental Biology (CDB) Laboratory for Cell Migration, under team leader Kiyoji Nishiwaki, has demonstrated the role of a protein modification known as glycosylation in guiding the migration of gonadal cells in the nematode, C. elegans.

This study, conducted in collaboration with researchers from the Japanese National Institute of Advanced Industrial Science and Technology, and the Universities of Nagoya (Japan) and Toronto (Canada), is the first to reveal the function of glycosylation in the action of an ADAM-family protease, a finding of potential significance to the study and treatment of human autoimmune diseases and other disorders that involve defects in ADAM-family protein function.

Interactions between the basement membrane of the migrating gonad and that of the body wall are one of the keystone processes of gonadal development. The C. elegans gonad is U-shaped, the result of the directed migration of cells known as distal tip cells present at the leading ends of the developing gonad in larvae. The gene mig-17, which Nishiwaki previously showed to be essential to this guided movement, is expressed in muscle cells and secreted into the body cavity where it binds to the migrating gonadal tip cells. Distal tip cells in worms engineered to lack the MIG -17 protein fail to steer cell migration properly, resulting in abnormal development and a emeanderingf gonad phenotype. However, the means by which MIG-17 coordinates the timing and direction of the developing gonadfs progress though the larval body has remained unknown.

MIG-17 is an ADAM (a disintegrin and meta

Contact: Doug Sipp
RIKEN Center for Developmental Biology

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