Function of Carboxypeptidase D

描述（由申请人提供）：羧基肽酶D （CPD）被认为在传递分泌途径的蛋白质的生物合成途径中起作用，如胰岛素样生长因子和胰岛素受体。此外，CPD还（与羧基肽酶E一起）参与胰岛素等神经内分泌肽的加工。为了进一步研究CPD的功能，我们将实验系统从牛、大鼠和鸭转移到果蝇。首先，比较果蝇和哺乳动物CPD的序列和酶性质，可以反映出通过进化保守的关键要素。第二，有几个果蝇突变体在CPD上有缺陷（称为silver，或svr突变体）；这些提供了一个方便的体内系统来测试CPD的各个结构域的功能。

DESCRIPTION (provided by applicant): Carboxypeptidase D (CPD) is thought to function in the biosynthetic pathway of proteins that transit the secretory pathway, such as insulin-like growth factor and the insulin receptor. In addition, CPD also participates (along with carboxypeptidase E) in the processing of neuroendocrine peptides such as insulin. To further study the function of CPD, we have shifted our experimental system from bovine, rat, and duck to that of Drosophila for several reasons. First, a comparison of the sequence and enzymatic properties of Drosophila CPD with those of mammalian CPD provides a reflection of the key elements that have been conserved through evolution. Second, there are several Drosophila mutants with defects in CPD (named silver, or svr mutants); these provide a convenient in vivo system to test the function of the various domains of CPD. The Specific Aims are: (1) To study the properties and distribution of Drosophila CPD; (2) To determine the molecular basis of the svr mutants and the consequence of these mutations on the expression and enzymatic properties of CPD; (3) To determine the function of the different domains of CPD by expressing specific forms in the svr mutants; and (4) To examine the consequences of the various CPD mutants (and transgenic flies with specific forms of CPD) on the processing of peptides and proteins. Taken together, these studies will provide an understanding of the biological role of CPD. The high degree of conservation of CPD between Drosophila and mammals suggests that the basic domain structure of CPD is critical for its function. The overall goal of this proposal is to understand the role of each domain within CPD, using a simple organism for which CPD mutants exist and which is amenable to transgenic analysis.