Dissertation
The role of mitotic motor forces of KIFC1 on microtubule array during neurodevelopment
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2020
DOI:
https://doi.org/10.17918/00000318
Abstract
The pattern of organization of microtubules plays a significant role in the polarization of neurons, which enables neurons to migrate, axons to elongate and growth cones to navigate. These patterns are established and maintained by motor proteins (dynein and kinesins) that impose forces on short and long neuronal microtubules. KIFC1 (also called HSET or kinesin-14a) belongs to Kinesin-14 family, an unusual group of kinesins that like cytoplasmic dynein move towards the minus end of the microtubule but additionally has specialized microtubule crosslinking properties. Despite KIFC1's high expression in both embryonic and adult neurons, its functional role in neurodevelopment remains unexplored. Experimental manipulations of KIFC1 in vitro and in vivo early in neurodevelopment elicit defects in neuronal migration, as well as morphological changes in axonal outgrowth. Our data suggest that in neuronal migration, KIFC1 crosslinks microtubules in the soma, facilitating dynein to thrust the soma forward, by providing midcourse corrections that keep the migrating neuron on its appropriate trajectory. Moreover, in axon outgrowth, we conclude that the major role of KIFC1 in the axon is to crosslink microtubules in a manner that resists their capacity to slide, especially in the distal region of the axon where forces such as the retrograde flow of actin filaments may otherwise push microtubules backward. Mechanistically our data indicate that KIFC1 organizes the microtubule ensemble in neurons by binding to microtubules and sliding them into alignment in an ATP-dependent fashion and then crosslinking them in an ATP-independent fashion.
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Details
- Title
- The role of mitotic motor forces of KIFC1 on microtubule array during neurodevelopment
- Creators
- Hemalatha Muralidharan
- Contributors
- Peter W. Baas (Advisor) - Drexel University, Neurobiology and Anatomy
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 158 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Other Identifier
- 991014855446504721