University of Illinois Urbana-Champaign

Primordial imperatives and the evolution of control of endolysosomal trafficking

Lawrence, Gus

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LAWRENCE-DISSERTATION-2017.pdf

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https://hdl.handle.net/2142/97259

Description

Title
Primordial imperatives and the evolution of control of endolysosomal trafficking
Author(s)
Lawrence, Gus
Issue Date
2017-04-20
Director of Research (if dissertation) or Advisor (if thesis)
Fratti, Rutilio
Doctoral Committee Chair(s)
Fratti, Rutilio
Committee Member(s)
  • Morrisey, James
  • Gennis, Robert
  • Chen, Jie
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2017-08-10T19:14:28Z
Keyword(s)
  • Vesicular trafficking
  • Endosomes
  • Guanine nucleotide exchange factors (GEFs)
  • Endosomal trafficking
  • Nutrient sensing
  • Membrane integrity
  • Membrane dynamics
Abstract
Lysosomes solve fundamental obstacles to the evolution of complex life forms. Lysosomes sense and maintain cellular metabolic stores and ensure their judicious use. More importantly, lysosomes respond to changes in osmotic conditions to maintain the membrane, which protects life from the harsh realities of the second law of thermodynamics. The primordial imperatives of the first and second law of thermodynamics underlie the evolution of the processes regulating membrane traffic. In order to meet the needs of maintenance of membrane integrity and osmotic stress with energy production, the endo-lysosomal fusion machinery integrates information from the metabolic and osmotic state of the cell to regulate fusion activity of the endosome and receptor recycling. Membrane lipids orchestrate the processes of endo-lysosomal maturation. This Dissertation identified lipid modifiers that regulate endolysosomal maturation in response to metabolism and osmotic stress. We then manipulated these conditions in order to probe how the membrane lipid environment controls the subunit associations and function of the endo-lysosomal machinery and the guanine nucleotide exchange factor Mon1-Ccz1 Endo-lysosomal dynamics have evolved to impact diverse physiological processes including, retrograde axonal transport(Deinhardt et al., 2006), and immune activation and antigen loading on MHC-II(Fairn and Grinstein, 2012) and cellular signaling systems such as insulin(Lodhi et al., 2008) and Wnt(Taelman et al., 2010). By examining the mechanisms of control in their evolutionary context, one gains a better understanding of a complicated cellular process underlying diseases such as autoimmunity, Alzheimer’s disease, and Diabetes Mellitus.
Graduation Semester
2017-05
Type of Resource
text
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http://hdl.handle.net/2142/97259
Copyright and License Information
Copyright 2017 Gus Lawrence

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Dissertations and Theses - Biochemistry
Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois