Neurons alter endoplasmic reticulum exit sites to accommodate dendritic arbor size
Abstract/Contents
- Abstract
- Nervous systems consist of neurons with a wide range of form and function. This neural diversity is critical for nervous system function. How neurons achieve such diverse morphologies has been a central question in neuroscience since its inception. Neurite outgrowth is regulated on several levels. First, a neurite's particular shape is determined by guidance receptors on the neurite surface interacting with environmental ligands to inform neurite pathfinding. Second, intracellular cytoskeleton is coordinated by these guidance receptors to generate the force required for neurite progress through the sub-strate. Third, a neuron must coordinately scale its biological processes, such as biosyn-thesis and secretion, to supply sufficient building blocks, including lipids and surface proteins, for its expanding surface area. Considerable work has been done to elucidate mechanisms of neurite pathfinding and force generation. However, relatively little is known about how neurons scale biosynthetic and secretory machinery to accommodate cell membranes of vastly different size. Using the nematode Caenorhabditis elegans (worm), we observed that neurons with larg-er plasma membranes displayed higher numbers of the early secretory organelles, Endo-plasmic Reticulum Exit Sites (ERESs). ERES function is required for dendrite growth and ERES size and number are intimately linked with the biosynthetic and secretory flux of non-neuronal cells. However, how neurons of different size scale secretory machinery, such as ERESs, to meet vastly differing growth requirements is not known. Using timelapse microscopy, we show that the worm's largest neuron, PVD, has espe-cially high ERES numbers, which are initially established during neuron birth via asym-metric cell division. We show that maintenance of PVD's high ERES number during neu-ron development does not require normal dendrite outgrowth, but depends on cell fate transcription factors, nutrient availability, and master growth regulator ceTOR/LET-363. Together these factors coordinately maintain ERES number and somato-dendritic growth throughout PVD development. Our data suggest a model in which cell fate transcription factors drive both asymmetric cell division and subsequent nutrient sensor levels to set the biosynthetic output that specifies ERES number and cell size. This work takes a first step toward identifying the mechanisms regulating neuronal bio-synthetic and secretory output, and highlights several advantages and challenges of pur-suing novel mechanisms for cell-specific size and organelle scaling in multicellular or-ganisms.
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 | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Land, Ruben Helmut |
|---|---|
| Degree supervisor | Shen, Kang, 1972- |
| Thesis advisor | Shen, Kang, 1972- |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Thesis advisor | Luo, Liqun, 1966- |
| Thesis advisor | Skotheim, Jan, 1977- |
| Degree committee member | Clandinin, Thomas R. (Thomas Robert), 1970- |
| Degree committee member | Luo, Liqun, 1966- |
| Degree committee member | Skotheim, Jan, 1977- |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Neurosciences Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ruben Land. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/fn480nv6926 |
Access conditions
- Copyright
- © 2023 by Ruben Helmut Land
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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