Intrinsic and extrinsic factors influencing presynapse number and location in C. elegans
Abstract/Contents
- Abstract
- The number of connections formed between neurons and their targets is dynamic. In vertebrate systems the number peaks in young animals and then reduces with age. Throughout life, the connections are plastic and can change in response to activity. Misregulation of synapse number is associated with mental retardation and some degenerative diseases. Few studies have focused on using an in vivo system with a stereotyped synaptic circuit to understand the mechanisms regulating synapse number. To better understand factors influencing synapse number we studied the C.elegans motorneuron DA9, which has a highly stereotyped number and location of synapses. We found that loss of function of the myotubularin family member mtm-6 reduces the number of synapses in the DA9 motorneuron. MTM-6 is a lipid phosphastase whose human homologs MTMR 6-8 are capable of acting on phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. We found that mtm-6 is expressed in nervous system of the worm as well as the previously reported tail cells. The reduction of synapse number is due to two different functions of MTM-6 reflected by its expression pattern. MTM-6 regulates secretion of the C. elegans Wnt ligand EGL-20 in a fairly specific manner due in part to their mutual expression in non-neuronal tail cells. Loss of egl-20 causes a reduction in synapse number that appears to be the result of DA8 and DA9 maintaining a synaptic border. While mtm-6 regulation of egl-20 is non-autonomous, mtm-6 also causes a reduction in synapse number due to intrinsic mechanisms in the neuron. MTM-6 impacts endocytosis through its dephosphorylation of phosphatidylinositol 3-phosphate. In the process of studying whether or not synapse number was impacted in endocytosis and exocytosis mutants we discovered that these mutants affect the localization of presynaptic material. unc-26/synaptojanin caused synaptic vesicle puncta to localize into the normally synapse-free region of DA9. This phenotype was not observed in the alleles used for other endocytosis mutants, such as unc-57/endophilin, itsn-1/intersectin, amph-1/amphiphysin, or dyn-1/dynamin. In contrast loss of the exocytosis genes unc-13/Munc-13 or unc-18/Munc-18 caused mislocalization of presynaptic material to the dendrite. The mislocalization phenotype of unc-13/Munc-13 was suppressed by loss of unc-57/endophilin. Our results indicate that proper distribution of presynaptic material is impaired in different ways depending on which part of the synaptic vesicle cycle is targeted.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Ericson, Vivian Russell | |
|---|---|---|
| Associated with | Stanford University, Department of Molecular and Cellular Physiology. | |
| Primary advisor | Shen, Kang, 1972- | |
| Thesis advisor | Shen, Kang, 1972- | |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- | |
| Thesis advisor | Meyer, Tobias | |
| Thesis advisor | Smith, Stephen | |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- | |
| Advisor | Meyer, Tobias | |
| Advisor | Smith, Stephen |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Vivian Russell Ericson. |
|---|---|
| Note | Submitted to the Department of Molecular and Cellular Physiology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Vivian Russell Ericson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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