Heterogenous dynamics and mechanisms of mammalian primary cilia disassembly
- Mariya Mirvis.
- [Stanford, California] : [Stanford University], 2019.
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- ["Primary cilia are sensory signaling organelles critical in the regulation of cell proliferation and development. Assembly and disassembly of cilia are complex processes, closely linked with, and essential for, ciliary function and cell cycle progression. However, mechanisms and dynamics of ciliary disassembly are poorly understood in mammalian systems. We characterized dynamics and behaviors of ciliary disassembly in IMCD3 cells. Disassembly behaviors were classified into three major modes, varying in rate by two orders of magnitude -- gradual ciliary shortening, instant loss, and combined behavior consisting of consecutive gradual and instant stages. Surprisingly, instant loss ultimately accounts for a significant majority of disassembly events. We developed two distinct methods of isolating ciliary material from culture media following induction of ciliary disassembly. Consistent recovery of cilia-like structures by both methods demonstrates that instant loss is likely due to deciliation. Two candidate regulators of deciliation were examined -- katanin, and intracellular calcium. Overexpression of the katanin catalytic domain p60 leads to reduced ciliary length and stronger preference toward Instant disassembly dynamics, independently of calcium perturbations. Thus, mammalian ciliary disassembly involves a tunable decision between deciliation and resorption. We propose a model for ciliary disassembly involving two distinct decision points: 1) whether and when to disassemble the cilium, and 2) by which mechanism to disassemble the cilium."]
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- Submitted to the Department of Molecular and Cellular Physiology.
- Thesis Ph.D. Stanford University 2019.