University of Illinois at Chicago
Browse

File(s) under embargo

2

month(s)

14

day(s)

until file(s) become available

A Novel Regulatory Role of Tomosyn in HOPS-dependent Endo-lysosomal Function in C. elegans Coelomocytes

thesis
posted on 2022-08-01, 00:00 authored by Kristin Gallik
Intracellular membrane fusion events between endosomes, lysosomes, and autophagosomes are critical to maintaining cellular health. Dysfunction of these steps can lead to severe functional defects such as cognitive impairments and premature death. We previously identified VPS-39 as a binding partner of the WD40-repeat domains of C. elegans Tomosyn in a yeast two-hybrid assay. Tomosyn is a known inhibitor of exocytic membrane fusion and prevents excessive neurotransmitter release. VPS-39 is a member of the HOPS complex which is essential for mediating endomembrane fusion and embryonic survival. The interaction of these proteins revealed a potential novel role for Tomosyn in regulating endomembrane fusion. In this thesis, we characterize the novel relationship of VPS-39 and Tomosyn in regulating endomembrane fusion events in C. elegans coelomocytes. We hypothesized that Tomosyn and VPS-39 function together at the junction of late endosomes and lysosomes to regulate the fusion of these organelles. Our investigation of this hypothesis using fluorescence markers and ultrastructural data provides evidence to support our proposed mechanism. Additionally, this body of work provides the first reported analysis of entire coelomocytes using ultrathin serial sections, the first evidence that Tomosyn functions in regulating endomembrane fusion events, and that VPS-39 displays in vivo RAB-7 GEF activity.

History

Advisor

Richmond, JanetPark, Thomas

Department

Biological Sciences

Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Orenic, Teresa Warpeha, Katherine Alford, Simon Esquibel, Corinne

Submitted date

August 2022

Thesis type

application/pdf

Language

  • en

Usage metrics

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC