Abstract

This application has three main goals. In the first goal, Dr. Balch's group proposes to extend their high-resolution structural analysis of GDIs. They propose to solve several structures that include the structure of the related beta GDI, the structure of Rab3A in the GDP form, to determine the structure of the geranyl lipid binding site in alpha GDI and to solve the structure of a complex made of alpha GDI and Rab3A. This part of the project is a continuation of a fruitful collaboration with the group of Dr. I. Wilson at Scripps. The second goal is to identify the membrane protein(s) involved in the recruitment to and retrieval from GDI to membranes that are required during the process of vesicle formation and fusion. These studies will be based on biochemical approaches and are built on the hypothesis that domain II of GDI uses a mobile loop as the effector domain for these interactions. The third goal is to study the role of GSI, Rab3A and other possible interacting proteins in the process of vesicle delivery during exocytosis. Dr. Balch will use an in vitro, semi-intact synaptosome assay recently developed by his group to explore the functional role of these proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033301-21
Application #
6661352
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Shapiro, Bert I
Project Start
1992-07-01
Project End
2004-09-02
Budget Start
2003-09-01
Budget End
2004-09-02
Support Year
21
Fiscal Year
2003
Total Cost
$340,168
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Rauniyar, Navin; Subramanian, Kanagaraj; Lavallée-Adam, Mathieu et al. (2015) Quantitative Proteomics of Human Fibroblasts with I1061T Mutation in Niemann-Pick C1 (NPC1) Protein Provides Insights into the Disease Pathogenesis. Mol Cell Proteomics 14:1734-49
Roth, Daniela Martino; Hutt, Darren M; Tong, Jiansong et al. (2014) Modulation of the maladaptive stress response to manage diseases of protein folding. PLoS Biol 12:e1001998
Hutt, Darren M; Balch, William E (2013) Expanding proteostasis by membrane trafficking networks. Cold Spring Harb Perspect Med 3:1-21
Powers, Evan T; Balch, William E (2013) Diversity in the origins of proteostasis networks--a driver for protein function in evolution. Nat Rev Mol Cell Biol 14:237-48
Pottekat, Anita; Becker, Scott; Spencer, Kathryn R et al. (2013) Insulin biosynthetic interaction network component, TMEM24, facilitates insulin reserve pool release. Cell Rep 4:921-30
Hutt, Darren M; Balch, William E (2013) Expanding proteostasis by membrane trafficking networks. Cold Spring Harb Perspect Biol 5:
Powers, Evan T; Balch, William E (2013) Diversity in the origins of proteostasis networks--a driver for protein function in evolution. Nat Rev Mol Cell Biol 14:237-48
Bouchecareilh, M; Balch, W E (2012) Proteostasis, an emerging therapeutic paradigm for managing inflammatory airway stress disease. Curr Mol Med 12:815-26
Bouchecareilh, Marion; Hutt, Darren M; Szajner, Patricia et al. (2012) Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of ýý1-antitrypsin deficiency. J Biol Chem 287:38265-78
Hulleman, John D; Kaushal, Shalesh; Balch, William E et al. (2011) Compromised mutant EFEMP1 secretion associated with macular dystrophy remedied by proteostasis network alteration. Mol Biol Cell 22:4765-75

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