Detection of signals is critical for the function of eukaryotic cells. D. discoideum cells are particularly adept at responding chemical gradients, sensing single percent concentration changes across their body. We measure the ability of the cells to sense gradients through this developmental transition as they change their internal machinery. Additionally, we impair the ability of the cells to modulate the speed of the receptors and measure the effect of a single receptor state on gradient sensing over development.
We find a novel link between mechanotransduction and autophagy through the actin-rich microvillar protrusions lining the gut. These protrusions on the apical cell surface share structural similarities to the mechanosensitive stereocilia in the inner hair cells of the ear. Intestinal epithelial monolayers with microvilli, when exposed to persistent fluid shear stress, developed large vacuoles lined with autophagy associated proteins LC3 and LAMP1. The size and number of vacuoles were suppressed by perturbations to the autophagy pathway, including small molecule inhibitors and LC3 knockdown as well as through perturbations to the microvilli. Our results establish a link between apical shear and autophagic trafficking in intestinal epithelial monolayers.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-11182016-144522 |
| Date | 18 November 2016 |
| Creators | Ehrman, Jonathan David |
| Contributors | Erin Rericha |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-11182016-144522/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
Page generated in 0.0057 seconds