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Title page for ETD etd-03162016-135935


Type of Document Dissertation
Author Parkinson, William Matthew
Author's Email Address williammparkinson@yahoo.com
URN etd-03162016-135935
Title Synaptic Requirements for Glycan Modification
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Donna Webb Committee Chair
Donna Webb Committee Chair
Aurelio Galli Committee Member
Aurelio Galli Committee Member
Kendal Broadie Committee Member
Kendal Broadie Committee Member
Terry Page Committee Member
Terry Page Committee Member
Todd Graham Committee Member
Todd Graham Committee Member
Keywords
  • drosophila
  • neuromuscular junction
  • drosophila
  • synapse
  • neuromuscular junction
  • glycosylation
  • synapse
  • glycosylation
Date of Defense 2016-03-15
Availability unrestricted
Abstract
Glycosylation is the most common post-translational modification to proteins, involving the addition of chained sugars to regulate folding, localization and intermolecular interactions. Glycosylated proteins are most heavily concentrated on the extracellular side of cellular membranes, and most secreted proteins are glycosylated. Both of these glycoprotein classes are critical for cell-cell interactions, particularly during metazoan development. The nervous system is enriched for glycoproteins, and neurons appear dependent on glycosylation in the regulation of synapse structure and function. This thesis tests glycosylation roles at the synapse by analyses of two genes at the Drosophila neuromuscular junction (NMJ); mgat1 required to produce hybrid and complex glycan branches, and pmm2 required to produce all N-linked glycosylation. Loss of either gene results in defective synaptic glycosylation, and similarly overelaborated NMJ architecture and elevated neurotransmission. Moreover, both mutant conditions cause aberrant trans-synaptic signaling that normally directs the recruitment of synaptic proteins required for synaptogenesis and neurotransmission. Thus, synaptic glycosylation strongly modulates the trans-synaptic signaling that in turn drives the recruitment synaptic proteins that mediate of structural and functional synaptogenesis. This thesis produces a new genetic model for the heritable Congenital Disorders of Glycosylation (CDG) disease state CDG1a (a.k.a. PMM2-CDG), producing an avenue for the development of treatments and therapeutic interventions.
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