Investigating the molecular mechanisms of axon and dendrite regeneration in Drosophila peripheral neurons.
Open Access
- Author:
- Swope, Rachel
- Area of Honors:
- Biochemistry and Molecular Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Melissa Rolls, Thesis Supervisor
Ming Tien, Thesis Honors Advisor - Keywords:
- axon regeneration
dendrite regeneration
Drosophila melanogaster
Exocyst complex
endoplasmic reticulum
membrane - Abstract:
- Neurons must endure the lifetime of an organism, but their axons and dendrites are vulnerable to insults, including stoke, neurodegenerative disease, traumatic injuries to the brain and spinal cord, anticancer drugs, and infection. Neurons in the PNS have evolved robust mechanisms to regenerate a damaged axon or dendrite(s). Molecular mechanisms for dendrite regeneration remain undefined, so I performed a candidate-based screen of protein traps and Gal4-enhancer traps to find a reporter for dendrite regeneration. I also studied how plasma membrane (PM) expansion is polarized during axon regeneration. Smooth endoplasmic reticulum (SER) is enriched at the tip of regenerating axons but not regenerating dendrites, so I hypothesized that the SER is a site of local lipid synthesis here and adds lipids to the PM via non-vesicular transport at membrane contact sites. The alternate hypothesis is that the bulk of new PM is added via Exocyst-dependent polarized secretion of post-Golgi vesicles. SER could provide Ca2+ to trigger the fusion of these vesicles with the PM at the regenerating axon tip. I found that the ER-PM lipid transfer protein, extended synaptotagmin 2 (ESyt2), is not enriched in the SER at the tip of the regenerating axon. Instead, I found that the Exocyst complex is essential for axon regeneration and several other forms of neurite outgrowth. My findings support the hypothesis that most new PM comes from Exocyst-dependent secretion of post-Golgi vesicles rather than non-vesicular lipid transfer at ER-PM membrane contact sites.