The Myosin-Binding UCS Domain but not the Hsp90-Binding TPR Domain of the UNC-45 Chaperone is Essential for Myosin Accumulation and Assembly in Caenorhabditis elegans
| dc.contributor.advisor | Perez-Polo, Jose R | |
| dc.contributor.committeeMember | Epstein, Henry F | |
| dc.contributor.committeeMember | May, Greg S | |
| dc.contributor.committeeMember | Boehning, Darren F | |
| dc.contributor.committeeMember | Barral, Jose M | |
| dc.creator | Ni, Weiming | |
| dc.date.accessioned | 2016-11-01T18:12:27Z | |
| dc.date.available | 2016-11-01T18:12:27Z | |
| dc.date.created | 2011-12 | |
| dc.date.submitted | December 2011 | |
| dc.date.updated | 2016-11-01T18:12:27Z | |
| dc.description.abstract | The UNC-45 family of molecular chaperones is expressed in metazoan organisms from C. elegans to humans. The UNC-45 protein is essential in C. elegans for early body-wall muscle cell development and A band assembly. We show that the myosin-binding UCS domain of UNC-45 alone is sufficient to rescue embryonic lethal unc-45 null mutants arrested in embryonic muscle development and temperature-sensitive loss-of-function unc-45 mutants defective in worm A band assembly. Removal of the Hsp90-binding TPR domain of UNC-45 does not affect rescue. Similar results were obtained with overexpression of the same fragments in wild-type nematodes when assayed by diminution of myosin accumulation and assembly. Titration experiments show that on a per molecule basis, UCS has greater activity in C. elegans muscle in vivo than full-length UNC-45 protein, suggesting it may be inhibited by either the TPR domain or its interaction with the general chaperone Hsp90. In vitro experiments with purified recombinant C. elegans Hsp90 and UNC-45 proteins show that they compete for binding to C. elegans myosin. Our in vivo genetic and in vitro biochemical experiments are consistent with a novel inhibitory role for Hsp90 with respect to UNC-45 action. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/2152.3/786 | |
| dc.subject | UNC-45 | |
| dc.subject | Hsp90 | |
| dc.subject | Myosin | |
| dc.subject | Assembly | |
| dc.subject | Accumulation | |
| dc.subject | Worm | |
| dc.title | The Myosin-Binding UCS Domain but not the Hsp90-Binding TPR Domain of the UNC-45 Chaperone is Essential for Myosin Accumulation and Assembly in Caenorhabditis elegans | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Biochemistry and Molecular Biology | |
| thesis.degree.discipline | Biochemistry and Molecular Biology | |
| thesis.degree.grantor | The University of Texas Medical Branch at Galveston | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Biochemistry and Molecular Biology (Doctoral) |