This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.It is clear that the tolloid family of metalloproteases play an important role in embryonic patterning and tissue morphogenesis during embryogenesis. Evidence suggests that the tolloids facilitate the activity of neurotrophic factors such as the BMPs and may function in regulation of neurogenesis and mechanisms of synaptic plasticity. Our preliminary data show that expression of turtle tolloid-like gene (tT11) is significantly upregulated during conditioning compared to pseudoconditioned controls in vitro brain stem preparations. What are the mechanisms of action of tolloid-like genes, specifically tTLL. We hypothesize that tTLL can potentiate the activity of transforming frowth factor-B (TGF-B) family member, by antagonizing Chrodih, and/or tTLL can act by different mechanisms (tTLL can be involved in receptor trafficking or it can interact with some extacellular matrix component). To understand this question we will try to get two recombinant tTLL proteins (active and inactive) and perform in vitro cleavage assay of these two tTLLs with Chordih. These two aims will help us to achiee our next aim: to identify protein interaction with turtle tolloid-like protein.
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