OSTEOBLAST MEDIATED TURNOVER OF COLLAGENASE IN BONE

描述（改编自申请人的摘要）： 研究员，Nicola Parkman，博士，建议研究 再吸收酶的结合、内化和降解， 胶原酶-3（也称为，金属蛋白酶13，MMP-13）， 从成骨细胞中分离出来据推测，有一个 特异性受体，胶原酶-3受体，其与胶原酶-3结合， 导致胞吞作用，触发胶原酶-3的进一步相互作用， 低密度脂蛋白受体相关蛋白（LRP）。的精确 因此，MMP-3的生物活性取决于浓度的平衡。 它的分泌和受体介导的摄取之间的联系。根据初步 根据推定受体可能是新的凝集素的数据，申请人提出 四个具体目标。首先，她建议表达和审查条例 胶原酶-3受体。其次，她建议突变受体， 确定其与胶原酶-3相互作用的功能结构域。第三，她 将研究胶原酶-3分子与LRP的相互作用。最后她 提出确定胶原酶-3分子的结构域， 胶原酶-3受体和LRP受体。关于《公约》执行情况的重要新资料 这一重要分子的生物学可能来自这些研究。

DESCRIPTION (Adapted from the Applicant's Abstract): The principal investigator, Nicola Partridge, Ph.D., proposes to examine the mechanism of the binding, internalization and degradation of the resorptive enzyme, collagenase-3 (a.k.a., metalloproteinase 13, MMP-13) following its elaboration from the osteoblast during resorption. It is hypothesized that there is a specific receptor, the collagenase-3 receptor, which binds to collagenase-3, resulting in endocytosis that triggers a further interaction of collagenase-3 with the low-density lipoprotein receptor-related protein (LRP). The precise concentration, and hence, the biological activity of MMP-3 depends on a balance between its secretion and its receptor-mediated uptake. Based upon preliminary data that the putative receptor may be a novel lectin, the applicant proposes four Specific Aims. First, she proposes to express and examine the regulation of the collagenase-3 receptor. Secondly, she proposes to mutate the receptor to determine its functional domains that interact with collagenase-3. Thirdly, she will study the interaction of the collagenase-3 molecule with LRP. Finally, she proposes to determine the domains of the collagenase-3 molecule that bind the collagenase-3 receptor and the LRP receptor. Critical new information on the biology of this important molecule may be derived from these studies.