{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/786"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/786","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"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","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Ni, Weiming"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Biochemistry and Molecular Biology (Doctoral)","degree_level":"Doctoral","degree_discipline":"Biochemistry and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Perez-Polo, Jose R"],"committee_chairs":[],"committee_members":["Epstein, Henry F","May, Greg S","Boehning, Darren F","Barral, Jose M"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:51:06Z","subjects":["UNC-45","Hsp90","Myosin","Assembly","Accumulation","Worm"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/786","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Perez-Polo, Jose R"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Epstein, Henry F","May, Greg S","Boehning, Darren F","Barral, Jose M"]},{"key":"dc:creator","label":"Author","values":["Ni, Weiming"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-11-01T18:12:27Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-11-01T18:12:27Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Biochemistry and Molecular Biology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["UNC-45","Hsp90","Myosin","Assembly","Accumulation","Worm"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/786"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["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"]}]}],"canonical_facts":{"dc:contributor.advisor":["Perez-Polo, Jose R"],"dc:contributor.committeemember":["Epstein, Henry F","May, Greg S","Boehning, Darren F","Barral, Jose M"],"dc:creator":["Ni, Weiming"],"dc:date.accessioned":["2016-11-01T18:12:27Z"],"dc:date.available":["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","Hsp90","Myosin","Assembly","Accumulation","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"],"thesis:degree_discipline":["Biochemistry and Molecular Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Biochemistry and Molecular Biology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:06Z"}