Regulation of membrane trafficking controls dendritic patterning
Abstract/Contents
- Abstract
- The construction of a large dendritic arbor requires robust growth and the precise delivery of membrane and protein cargoes to specific subcellular regions of the developing dendrite. How the microtubule-based vesicular trafficking and sorting systems are regulated to distribute these dendritic development factors throughout the dendrite is not well understood. We identified the small GTPase RAB-10, a conserved recycling endosome protein, and the exocyst complex as critical regulators of dendrite morphogenesis and patterning in the C. elegans sensory neuron PVD. In rab-10 and exocyst mutants, PVD dendritic branches are reduced in the posterior region of the cell but are excessive in the distal anterior region of the cell. In these mutants, multiple dendrite receptors are missing from the plasma membrane and are instead trapped in late endosomes. We also demonstrate that the dendritic branch distribution within PVD depends on the balance between the molecular motors kinesin-1/UNC-116 and dynein, and we propose that RAB-10 regulates dendrite morphology by balancing endosomal traffic to appropriately distribute branching factors, including the transmembrane receptor DMA-1. After characterizing the role of RAB-10 as an essential regulator of dendritic growth and patterning, we performed a forward genetic suppressor screen and identified the chromatin remodeling factors SIN-3 and HDA-3, two members of a histone deacetylase complex (HDAC), as regulators of RAB-10-independent membrane trafficking. Loss of SIN-3 or HDA-3 robustly suppresses the dramatic dendritic branch phenotype caused by loss of RAB-10 and the exocyst. The loss of SIN-3 or HDA-3 cannot resolve all trafficking defects observed in the rab-10 mutant, as membrane proteins still accumulate in intracellular vesicles in the rab-10 sin-3 or rab-10 hda-3 double mutants. However, the inactivation of SIN-3 or HDA-3 greatly increases the population of membrane receptor, leading to the suppression of the rab-10 mutant branching phenotype. Additionally, the inactivation of SIN-3 or HDA-3 results in a decrease of late endosomes and a possible reduction in degradation of membrane proteins. This surprising result provides a link between the inactivation of HDACs and endolysosomal signaling and indicates the PVD neuron is able to activate alternative membrane trafficking pathways to compensate for the loss of RAB-10-based trafficking. We hypothesize that chromatin remodeling by HDACs controls the choice between alternate neuronal states that utilize distinct membrane trafficking programs to support elaborate dendritic growth.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Taylor, Caitlin Ann |
|---|---|
| Degree supervisor | Shen, Kang, 1972- |
| Thesis advisor | Shen, Kang, 1972- |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Goodman, Miriam Beth |
| Thesis advisor | Luo, Liqun, 1966- |
| Degree committee member | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Degree committee member | Goodman, Miriam Beth |
| Degree committee member | Luo, Liqun, 1966- |
| Associated with | Stanford University, Neurosciences Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Caitlin Ann Taylor. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Caitlin Ann Taylor
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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