Mechanisms underlying PTP sigma-mediated synaptic differentiation and neuronal diversity
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Bomkamp, Claire
issued: 2019-04-17T16:24:20Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Brain function is dependent on both the properties of the individual neurons of which it is made up, as well as the precise pattern of connections between them. Both aspects of brain circuitry are determined in large part by the expression of specific genes. The products of these genes, including adhesion molecules, ion channels, and transcription factors, go on to shape neuronsâ properties and as well as their connectivity. Neurons direct their connectivity in part by expressing trans-synaptic cell adhesion molecules, which act as âmolecular velcroâ in order to form physical connections between axons and dendrites. These adhesion molecules are able to recruit the necessary components for synaptic transmission, through mechanisms which are incompletely understood. Chapter 2 focuses on one presynaptic adhesion molecule, PTPÏ, and its interaction with intracellular scaffolding proteins. PTPÏ is a phosphatase, but I found that its phosphatase activity is not needed for its ability to induce new synapses. However, interaction with the presynaptic scaffolding protein liprin-α is required. Because liprin-α binds to multiple presynaptic components, this finding suggests a mechanism through which PTPÏ recruits liprin-α to nascent synapses, and liprin-α in turn recruits other components, eventually leading to recruitment of vesicles, calcium channels, and everything else necessary for functional presynaptic release. Phenotypes of individual neurons, including electrophysiological activity and morphology, are known to be under genetic control. However, given the number of genes expressed by one organism and the difficulty of experimentally exploring the consequences of loss of function of any one gene, our understanding of the molecular underpinnings of any particular phenotype remains incomplete. In Chapter 3, I took the approach of searching for correlations between gene expression and neuronal phenotypes in a publicly available dataset. I found that controlling for bro…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/69744
note: MECHANISMS UNDERLYING PTP SIGMA-MEDIATED SYNAPTIC DIFFERENTIATION AND NEURONAL DIVERSITYbyClaire BomkampB.A., Western Washington University, 2011A THESIS SUBMITTED IN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFDOCTOR OF PHILOSOPHYinTHE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES(Neuroscience)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)April 2019© Claire Bomkamp, 2019The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled:Mechanisms underlying PTPÏ-mediated synaptic differentiation and neuronal diversitysubmitted by Claire Bomkamp in partial fulfillment of the requirements forthe degree of Doctor of Philosophyin NeuroscienceExamining Committee:Dr. Ann Marie CraigSupervisor Dr. Shernaz BamjiSupervisory Committee Member Dr. Catharine RankinUniversity ExaminerDr. Joerg GsponerUniversity ExaminerAdditional Supervisory Committee Members:Dr. Timothy OâConnorSupervisory Committee MemberDr. Douglas AllanSupervisory Committee MemberiiAbstractBrain function is dependent on both the properties of the individual neurons of which it is made up, as well as the precise pattern of connections between them. Both aspects of brain circuitry are determined in large part by the expression of specific genes. The products of these genes, including adhesion molecules, ion channels, and transcription factors, go on to shape neuronsâ properties and as well as their connectivity.Neurons direct their connectivity in part by expressing trans-synaptic cell adhesion molecules, which act as âmolecular velcroâ in order to form physical connections between axons and dendrites. These adhesion molecules are able to recruit the necessary components for synaptic transmission, through mechanisms which are incompletely understood. Chapter 2 focuses on one presynaptic adhesion molecule, PTPÏ, and its interaction with intracellular scaffolding proteins. PTPÏ is a phosphatase, but I found…
has type: Thesis/Dissertation
date issued: 2019-05
is shown at: 10.14288/1.0378286
language: eng
degree discipline: Neuroscience
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-ShareAlike 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-sa/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/69744