Dissertation
The Role of Tropomodulin's Actin and Tropomyosin Binding Sites in Dendritic Morphology
Doctor of Philosophy (PhD), Washington State University
01/2016
Handle:
https://hdl.handle.net/2376/117453
Abstract
Neurons are morphologically complicated cells. In order to develop their immensely intricate shape, neurons coordinate the function of many structural proteins, such as actin. Actin is a monomeric (G-actin) protein which can polymerize into filaments (F-actin). F-actin serves many purposes in a cell including providing structural support for intracellular transport and forces for cellular motility. There are hosts of proteins which act upon and regulate actin. One way in which actin is regulated is through alteration of the rate of incorporation and loss of monomers from filaments. F-actin has two polar ends, a fast growing (barbed) end, and a slow growing (pointed) end. Tropomodulins (Tmod) are a family of proteins that cap pointed ends and prevent polymerization and depolymerization of actin monomers. There are three Tmod isoforms expressed in the brain, but little is known about their role in either neuronal development or disease.
The work presented in this thesis aims to answer some of the largest questions about Tmods in neurons. We explore the neuronal structures Tmods regulate and the functions Tmods use to regulate those structures. This dissertation describes work that shows Tmod1 and Tmod2 are regulators of both the dendritic arbor and dendritic spines while Tmod3 has minimal influence over these structures. We show that Tmod1 requires its tropomyosin binding sites while Tmod2 does not to modulate the dendritic arbor. Furthermore, we show that Tmod1 and Tmod2 require both of their actin binding sites regulate morphology. We show that Tmod3 to its leucine rich repeat domain is responsible for Tmod3’s different role in dendritogenesis. We also use structural techniques to explore the differences in structure between the three isoforms.
This work steps into the darkness around actin pointed end regulation in neuronal development. It situates Tmods as regulators of neuronal shape and identifies isoform-specific functions used in this process. In addition to expanding the fundamental understanding of pointed end regulation in neurons, this work also suggests the consequences of altered Tmod expression may have neurological diseases.
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Details
- Title
- The Role of Tropomodulin's Actin and Tropomyosin Binding Sites in Dendritic Morphology
- Creators
- Kevin Tyler Gray
- Contributors
- Alla S Kostyukova (Advisor)Gary A Wayman (Committee Member)Nehal Abu-Lail (Committee Member)Sarah Hitchcock-DeGregori (Committee Member)Edward Pate (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Chemical Engineering and Bioengineering
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 212
- Identifiers
- 99900581631901842
- Language
- English
- Resource Type
- Dissertation