lloprotease) protease, a family of secreted or membrane proteins first identified as components of various snake venoms, where they have hemorrhagic and anti-coagulatory effects. ADAM-family proteases have been implicated in a number of human physiological and pathological processes, including blood coagulation disorders, rheumatoid arthritis and asthma. These proteins act to proteolytically release membrane-bound growth factors or to disrupt components of extracellular matrices such as collagen and proteoglycans (which help to build skin and soft tissue), and their roles in development and differentiation are the focus of interest in many research labs.
Nishiwakifs team analyzed a number of mutations that result in aberrant gonadal phenotypes similar to those seen in mig-17 mutants, including the mutation of the gene that encodes MIG-23. This protein was found to be structurally related to nucleoside diphosphatases (NDPases), glycosylating proteins found in the Golgi apparatus, the intracellular processing center where proteins are modified, sorted and released from the cell. Glycosylation involves the addition of a sugar to a site on a protein chain, a post-translational modification whose roles are incompletely understood, but which is thought to serve a regulatory function in some signaling molecules. On further investigation, MIG-23 mutants showed reductions in NDPase activity. The wild-type MIG-23 protein successfully rescued yeast mutants for NDPase, lending solid support to the case for the NDPase nature of MIG-23.
The similarity between the MIG-23 and MIG-17 phenotypes suggested that the mutation of MIG-23 might result in abnormal MIG-17 glycosylation. Using gel electrophoresis, Nishiwaki and colleagues demonstrated that MIG-17 molecules in MIG-23 mutants had lower than normal molecular weights consistent with the loss of glycosylation, while immunoblotting studies confirmed that in these mutants MIG-17 failed to bind sugars at the normal lPage: 1 2 3 Related biology news :1
Contact: Doug Sipp
RIKEN Center for Developmental Biology
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