OSTEOBLAST MEDIATED TURNOVER OF COLLAGENASE IN BONE

描述(改编自申请人摘要)：委托人 研究人员尼古拉·帕特里奇博士建议研究 吸收酶的结合、内化和降解， 胶原酶-3(又名金属蛋白酶13，基质金属蛋白酶-13) 在吸收过程中从成骨细胞中释放。它被假设存在一个 特异性受体，胶原酶-3受体，与胶原酶-3结合， 导致内吞作用，从而触发胶原酶-3的进一步相互作用 与低密度脂蛋白受体相关蛋白(LRP)。精准的 浓度，因此，基质金属蛋白酶-3的生物活性取决于平衡 它的分泌和受体介导的摄取之间的关系。基于初步的 申请人提出，假定的受体可能是一种新的凝集素的数据 四个具体目标。首先，她建议对这一规定进行表述和审查 胶原酶-3受体。其次，她建议将受体突变为 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 建议确定与胶原酶-3分子结合的结构域 胶原酶-3受体和LRP受体。关键的新信息关于 这种重要分子的生物学可以从这些研究中衍生出来。

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.