Functional dissection of membrane contacts sites in neuronal health in C. elegans
In neurons, the endoplasmic reticulum (ER) extends throughout all cellular processes, forming multiple contacts with the plasma membrane (PM) to fine-tune neuronal physiology. In my thesis project, I used the C. elegans DA9 motor neuron as my model system to explore the molecular mechanisms that are...
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| Format: | Thesis-Doctor of Philosophy |
| Language: | English |
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Nanyang Technological University
2023
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| Online Access: | https://hdl.handle.net/10356/166597 |
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| Institution: | Nanyang Technological University |
| Language: | English |
| Summary: | In neurons, the endoplasmic reticulum (ER) extends throughout all cellular processes, forming multiple contacts with the plasma membrane (PM) to fine-tune neuronal physiology. In my thesis project, I used the C. elegans DA9 motor neuron as my model system to explore the molecular mechanisms that are responsible for maintaining the distribution and function of neuronal ER-PM contact sites. I find that CIL-1 and ATLN-1 act together to maintain the somatodendritic enrichment of neuronal ER-PM contacts. Further, I show that the non-uniform distribution of ER-PM contact sites regulated by these proteins might be essential for efficient axon regeneration following a damaging insult. Finally, I provide evidence that ZC328.3 (the sole C. elegans homolog of GRAMD1 proteins, evolutionarily conserved sterol transporters that act at ER-PM contact sites) may contribute to cholesterol homeostasis in neurons. Collectively, my studies suggest that the maintenance of ER-PM contact sites is critical for maintaining neuronal health. |
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