====== Metalloproteinase ====== A metalloproteinase, or metalloprotease, is any [[protease]] [[enzyme]] whose catalytic mechanism involves a metal. An example of this would be meltrin which plays a significant role in the fusion of muscle cells during embryo development, in a process known as [[myogenesis]]. Most metalloproteases require [[zinc]], but some use [[cobalt]]. The [[metal]] ion is coordinated to the p[[rotein]] via three ligands. The ligands co-ordinating the metal ion can vary with [[histidine]], [[glutamate]], [[aspartate]], [[lysine]], and [[arginine]]. The fourth coordination position is taken up by a labile water molecule. Treatment with chelating agents such as EDTA leads to complete inactivation. EDTA is a metal chelator that removes zinc, which is essential for activity. They are also inhibited by the chelator orthophenanthroline. see [[Matrix metalloproteinase]]. ---- In a study, Sanz et al. identified a [[metalloproteinase]]-dependent mechanism necessary to promote growth in embryonic [[dorsal root ganglion]] cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 ([[ADAM10]]) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The [[IgLON]] family members [[Neurotrimin]] (NTM) and Limbic System-Associated Membrane Protein ([[LSAMP]]) were identified as ADAM10 substrates that are shed from the cell surface of [[Dorsal root ganglion]] (DRG) neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together this findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons ((Sanz RL, Ferraro GB, Girouard MP, Fournier AE. Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons. Sci Rep. 2017 Aug 11;7(1):7961. doi: 10.1038/s41598-017-08315-0. PubMed PMID: 28801670. )).