Class I myosins are monomeric actin-binding, ATP hydrolyzing molecular motors that are expressed in a variety of cell types, and function at the membrane-actin interface. Myosin-1d, one of eight vertebrate class I myosins, is expressed in polarized cells of the small intestine and nervous system, but subcellular localization and function for the motor remains largely unexplored. Intriguingly, myosin-1d is coexpressed in epithelial cells of the small intestine with myosin-a, where both motors target to the well-defined apical actin array of the brush border. However, how similar class I motors compartmentalize subcellularly is unknown, and raises the question of functional overlap. Interestingly, we found that myosin-1d and myosin1a exhibit differential localization and this partitioning can be explained by differential dynamics. Moreover, myosin-1d redistributes along the microvillar actin bundle in the absence of myosin-1a in MYO1A knockout animals. This suggests that class I myosins do have unique functions in wildtype, but may compensate for loss of activity. Interestingly, our data demonstrates that myosin-1d has a different subcellular localization in the nervous system. In these polarized cells, myosin-1d exhibits a punctate distribution in neuronal dendrites, cell bodies, and axons. We observed prominent expression in Purkinje cells and a subset of granule cells, with both patterns developmentally regulated. However, myosin-1d was not detectable in oligodendrocytes during early development. In the PNS, we observed that myosin-1d is present in neurons, and myelinating Schwann cells. This suggests a differential role for the motor in myelinating cells between the two nervous systems. Our studies also revealed that myosin-1d interacts with aspartoacylase, a catalytic enzyme involved in fatty acid synthesis that is widely expressed in similar polarized cells as myosin-1d. Together, these studies suggest that myosin-1d has distinct localization patterns in different polarized cell types, but may modulate aspartoacylase activity.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-12022011-134648 |
| Date | 12 December 2011 |
| Creators | Benesh, Andrew Eugene |
| Contributors | Matthew J. Tyska, David M. Miller, Christopher Janetopolous, Irina Kaverina, Bruce D. Carter, Robert J. Coffey |
| 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-12022011-134648/ |
| 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. |
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