To define the interactome of neuronal primary cilia

Whitmore, Brandon Alexander

To define the interactome of neuronal primary cilia

dc.contributor.advisor	Guo, Jiami
dc.contributor.advisor	Dufour, Antoine
dc.contributor.author	Whitmore, Brandon Alexander
dc.contributor.committeemember	Huang, Peng
dc.contributor.committeemember	Schriemer, David
dc.contributor.committeemember	Mains, Paul
dc.date	2021-11
dc.date.accessioned	2021-09-23T13:40:12Z
dc.date.available	2021-09-23T13:40:12Z
dc.date.issued	2021-09-17
dc.description.abstract	Primary cilia are projections of the plasma membrane on almost all mammalian cells in the body, including neurons. The purpose of primary cilia is to act as a cellular antenna due to the unique membrane composition of the primary cilia which is abundant in different receptors, like GPCRs and RTKs, and ion channels. Dysfunction of cilia signaling gives rise to a class of diseases known as ciliopathies. Ciliopathies present with brain structural and functional deficits and have been implicated in intellectual disabilities, Autism Spectrum Disorder, and Schizophrenia. While a number of ciliopathies have been determined, there is a gap in the knowledge of the mechanisms of some ciliopathies due to an incomplete understanding of the primary cilia proteome, especially within the brain. Understanding the primary cilia proteome may determine potential gene candidates that have been implicated in ciliopathies. The gap in the knowledge of the neuronal ciliary proteome arises from the difficulty in purifying mammalian primary cilia. Different proteomics techniques have been used to begin to study the primary cilia composition within kidney cells; however no techniques have been applied to neurons to study the proteome of neuronal primary cilia. The brain and kidneys respond to different extracellular cues and have different environments, indicating that neuronal primary cilia should have a unique membrane composition and respond to distinct extracellular cues compared to primary cilia of other cells. To identify the unique membrane composition of neuronal primary cilia I developed an in vitro proximity labeling method to isolate ciliary proteins from primary neuron cultures. From this work, I was able to create the first list of potential neuronal primary cilia proteins. As an alternative method to understand the membrane composition, I identified a number of signaling molecules that affect primary cilia morphology and impact signaling within cilia. These results will be used to begin constructing an interactome of neuronal primary cilia signaling.	en_US
dc.identifier.citation	Whitmore, B. A. (2021). To define the interactome of neuronal primary cilia (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.	en_US
dc.identifier.doi	http://dx.doi.org/10.11575/PRISM/39261
dc.identifier.uri	http://hdl.handle.net/1880/113944
dc.publisher.faculty	Cumming School of Medicine	en_US
dc.publisher.institution	University of Calgary	en
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.	en_US
dc.subject.classification	Neuroscience	en_US
dc.subject.classification	Health Sciences	en_US
dc.title	To define the interactome of neuronal primary cilia	en_US
dc.type	master thesis	en_US
thesis.degree.discipline	Medicine – Medical Sciences	en_US
thesis.degree.grantor	University of Calgary	en_US
thesis.degree.name	Master of Science (MSc)	en_US
ucalgary.item.requestcopy	false	en_US