Osiris Genes as Novel Coordinators of Protein Trafficking in Drosophila Trachea

Information

  • Research Project
  • 10291609
  • ApplicationId
    10291609
  • Core Project Number
    R15GM140376
  • Full Project Number
    1R15GM140376-01A1
  • Serial Number
    140376
  • FOA Number
    PAR-18-714
  • Sub Project Id
  • Project Start Date
    7/1/2021 - 3 years ago
  • Project End Date
    6/30/2024 - 5 months ago
  • Program Officer Name
    AINSZTEIN, ALEXANDRA M
  • Budget Start Date
    7/1/2021 - 3 years ago
  • Budget End Date
    6/30/2024 - 5 months ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    6/28/2021 - 3 years ago
Organizations

Osiris Genes as Novel Coordinators of Protein Trafficking in Drosophila Trachea

Summary Biological tubes with appropriate sizes are critical for the proper functioning of most major human organ systems (including but not limited to kidneys, lungs, and blood vessels). Malformation of tubes leads to various human diseases, such as polycystic kidney disease and vascular diseases. Drosophila trachea is the premier system to study the fundamental mechanisms underlying tubular organ formation. The Drosophila trachea is a ramifying network of epithelial tubes with a monolayer of epithelial cells surrounding an apical lumen. During tube expansion, the apical secretion burst deposits large amounts of luminal matrix components to the apical extracellular lumen. This process is critical for tube expansion to acquire mature sizes. Previous studies on apical secretion focused on the identification of components of the vesicular trafficking pathway involved in this process. As expected, in addition to endoplasmic reticulum and Golgi, a few endosomes are also required in this process. Instead of identifying additional trafficking components, the objective of this project is to reveal the ?broader coordination? of various trafficking components during apical secretion. This is a previously underappreciated mechanism in apical secretion in Drosophila trachea as well as in the overall field of vesicular trafficking. Our preliminary study on a poorly understood Osiris (Osi) gene family strongly indicates that Osi family genes function as ?traffic coordinators? to direct post-Golgi protein trafficking. In addition, a recent homology search revealed that Osi genes share noticeable sequence homology to glyoxalase 1 (Glo-1). Glo-1 is well known for its function in detoxification of methylglyoxal, a metabolic byproduct of glycolysis. It has been reported that Glo-1 plays a role in vesicular trafficking as well as morphological changes in blood vessels. These discoveries lead to a plausible hypothesis that they may also have some functional overlap in tubular organs. Our central hypothesis is that Osi genes function as ?traffic coordinators? to direct apical proteins by coordinated changes within secretion-related (e.g. endosomes, exosomes) and degradation-related trafficking components (e.g. lysosomes, autophagosomes). We will test this hypothesis by completing the following three specific aims: Aim. 1 Determine the function of Osi genes in apical secretion of the apical luminal matrix during tube expansion. Aim. 2: Determine the function of Osi genes as coordinators to increase numbers, volumes, activities of secretion-related trafficking components at the expense of degradation-related trafficking components in trachea. Aim. 3: Identify proteins that directly bind to Osi proteins. This project is significant because understanding the ?broader coordination? between various trafficking components will fill the gap in our understanding of the regulatory hierarchy in protein trafficking.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R15
  • Administering IC
    GM
  • Application Type
    1
  • Direct Cost Amount
    299089
  • Indirect Cost Amount
    139868
  • Total Cost
    438957
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIGMS:438957\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    DEV2
  • Study Section Name
    Development - 2 Study Section
  • Organization Name
    OAKLAND UNIVERSITY
  • Organization Department
    BIOLOGY
  • Organization DUNS
    041808262
  • Organization City
    ROCHESTER
  • Organization State
    MI
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    483094422
  • Organization District
    UNITED STATES