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MYOSIN-DEPENDENT TARGETING OF TRANSMEMBRANE PROTEINS IN
NEURONS
by
Tommy L Lewis Jr.
________________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR BIOLOGY)
August 2010
Copyright 2010 Tommy L Lewis Jr.
Object Description
| Title | Myosin-dependent targeting of transmembrane proteins in neurons |
| Author | Lewis, Tommy L., Jr. |
| Author email | tll@usc.edu; tll.usc@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Biology |
| School | College of Letters, Arts and Sciences |
| Date defended/completed | 2010-06-21 |
| Date submitted | 2010 |
| Restricted until | Restricted until 02 Feb. 2011. |
| Date published | 2011-02-02 |
| Advisor (committee chair) | Arnold, Donald B. |
| Advisor (committee member) |
Goodman, Steven Chen, Lin Wang, Pin |
| Abstract | In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Here we show that the plus end-directed motor Myosin Va plays a critical role in targeting of transmembrane proteins to dendrites. We show that Myosin Va is both necessary and sufficient to mediate the dendritic targeting of transmembrane proteins in dissociated rat cortical neurons. We also show that Myosin VI, a minus end-directed motor, mediates targeting of transmembrane proteins to the axon. In dissociated rat cortical neurons interaction with Myosin VI is both necessary and sufficient to mediate targeting of proteins to the axonal surface. Myosin VI mediates axonal targeting by causing endocytosis of proteins from the surface of dendrites and by facilitating direct targeting to the axon. In addition, interaction with either Myosin Va or Myosin VI is sufficient to target Channelrhodopsin 2 to dendrites or axons respectively in mice in vivo. We also provide evidence that an actin based vesicle filter exists at the axon initial segment, and that the filaments are oriented with their + end pointing out of the axon. Together, our results indicate that myosin-based mechanisms mediate dendritic as well as axonal targeting in neurons. |
| Keyword | myosin; neuron; dendritic targeting; cell biology; targeting; actin; Channelrhodopsin 2; vesicle filter |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3247 |
| Rights | Lewis, Tommy L., Jr. |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Lewis-3935 |
| Archival file | uscthesesreloadpub_Volume23/etd-Lewis-3935.pdf |
Description
| Title | Page 1 |
| Full text | MYOSIN-DEPENDENT TARGETING OF TRANSMEMBRANE PROTEINS IN NEURONS by Tommy L Lewis Jr. ________________________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR BIOLOGY) August 2010 Copyright 2010 Tommy L Lewis Jr. |
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