Functional dissection of membrane contacts sites in neuronal health in C. elegans

• Main Author: Nur Raihanah Binte Mohd Harion
• Other Authors: Yasunori Saheki
• Format: Thesis-Doctor of Philosophy
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Biological sciences::Molecular biology; Science::Biological sciences::Genetics
• Online Access: https://hdl.handle.net/10356/166597
• Institution: Nanyang Technological University

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.