New insights into neuronal polarity : actin waves and dynamic microtubule-based transport
- Neuron polarization is a fundamental process in the development of the nervous system. In vivo and in vitro, many types of neurons, including hippocampal neurons, transition from a multi-polar state with relatively identical, immature neurites, to a single axon state. During the multi-polar state, neurites seemingly stochastically retract and elongate while receiving different amounts of growth promoting factors via microtubule-based transport. A long-standing, unanswered question in the field is what controls fluctuating microtubule-based transport during neuronal polarity. In this thesis, we address this problem in several parts. First, we note that actin waves, waves of F-actin that move through neurites to promote neurite extension, are tightly linked to the fluctuating neurite lengths observed during the multi-polar phase. We performed further characterization of actin waves, showing that actin waves are under the control of small Rho GTPase activity and are composed of actively polymerizing actin. Because of the role of actin waves in controlling neurite length during the multi-polar phase, we then examined their role in mediating microtubule-based transport. Indeed, we found that actin waves serve to transiently increase microtubule-based transport by transiently increasing microtubule polymerization and number. We propose that actin wave promote microtubule polymerization by widening the neurite to create more space for already polymerizing microtubules. Finally, we offer preliminary data that suggests that retrograde movement of cargo during the multi-polar phase, which decreases a neurite's probability of becoming an axon, is driven by an increase in retrograde microtubule polymerization. As a whole, this thesis offers novel mechanisms for how dynamic microtubule-based transport is controlled during the multi-polar phase. It also proposes a new function for actin waves: in addition to mediating neurite outgrowth during the multi-polar phase, they also control anterograde microtubule-based transport, ensuring neurites grow out to explore their extracellular space to look for axon-promoting cues, as well as receive axon-promoting factors.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Biophysics Program.
|Statement of responsibility
|Submitted to the Program in Biophysics.
|Thesis (Ph.D.)--Stanford University, 2015.
- © 2015 by Amy Marie Winans
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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