Function of Carboxypeptidase D

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date5/15/964/30/10

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases: $83,500.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $234,321.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $227,524.00
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • National Institute of Diabetes and Digestive and Kidney Diseases: $221,581.00
  • National Institute of Diabetes and Digestive and Kidney Diseases

ASJC

  • Endocrine and Autonomic Systems
  • Genetics
  • Molecular Biology
  • Spectroscopy
  • Cell Biology

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