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Nhe6 and Nhe9 are sodium hydrogen exchangers found on separate mobile endosome populations in neuronal dendrites

Title:

Nhe6 and Nhe9 are sodium hydrogen exchangers found on separate mobile endosome populations in neuronal dendrites

Guterman, Mark (2013) Nhe6 and Nhe9 are sodium hydrogen exchangers found on separate mobile endosome populations in neuronal dendrites. Masters thesis, Concordia University.

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Abstract

This dissertation reports the endosomal locations of NHE6 and NHE9, sodium hydrogen exchangers that contribute to pathogenesis of Autism Spectrum Disorders (ASDs) within dendrites of cultured hippocampal neurons. ASDs are debilitating, neurological disorders characterized by deficient social interaction; obsessive, repetitive behaviors; and often accompanied by mental retardation, epilepsy, and attention deficit hyperactivity disorder (ADHD). For normal brain function to occur neurons form circuits at synapses and their size and strength change based on use, known as synaptic plasticity. Disruption of synaptic plasticity is thought to underlie ASDs. Because endocytosis is required for synaptic plasticity and the yeast ortholog of human Nhe6 and Nhe9 is known to contribute to this process, I hypothesized that Nhe6 and Nhe9 are found on endosomes in hippocampal neurons where they contribute to endocytosis and synaptic plasticity. Using fluorescence microscopy, I initially demonstrate that Nhe6 and Nhe9 are localized to different pools of endosomes with cultured HeLa cells using Rab-GTPases as markers of the endocytic pathway. Nhe6 and Nhe9 showed similar distribution within the dendrites of hippocampal neurons cultured from mice or rats whereby Nhe6 was present in Rab5 and Rab11-positive endosomes and Nhe9 was found in Rab11, Rab7, and Rab9-positive endosomes later in the pathway. Live neuron imaging revealed that both Nhe6 and Nhe9 endosomes are mobile and that Nhe9-positive endosomes appear to undergo transient fusion and fission events from Rab7, Rab9, or Rab11-positive endosomes. Together, these data imply roles for Nhe6 and Nhe9 in endosome mobility and fusion underlying endocytosis required for synaptic plasticity.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Guterman, Mark
Institution:Concordia University
Degree Name:M. Sc.
Program:Biology
Date:15 September 2013
Thesis Supervisor(s):Brett, Christopher
ID Code:977790
Deposited By: MARK GUTERMAN
Deposited On:26 Nov 2013 17:11
Last Modified:18 Jan 2018 17:45
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