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dc.contributor.authorStachelek, Stanley J.
dc.contributor.authorKowalik, Timothy F.
dc.contributor.authorFarwell, Alan P.
dc.contributor.authorLeonard, Jack L.
dc.date2022-08-11T08:08:48.000
dc.date.accessioned2022-08-23T16:09:02Z
dc.date.available2022-08-23T16:09:02Z
dc.date.issued2000-07-07
dc.date.submitted2009-01-13
dc.identifier.citationJ Biol Chem. 2000 Oct 13;275(41):31701-7. <a href="http://dx.doi.org/10.1074/jbc.M004221200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.M004221200
dc.identifier.pmid10882730
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32595
dc.description.abstractIn astrocytes, thyroxine modulates type II iodothyronine 5'-deiodinase levels by initiating the binding of the endosomes containing the enzyme to microfilaments, followed by actin-based endocytosis. Myosin V is a molecular motor thought to participate in vesicle trafficking in the brain. In this report, we developed an in vitro actin-binding assay to characterize the thyroid hormone-dependent binding of endocytotic vesicles to microfilaments. Thyroxine and reverse triiodothyronine (EC(50) levels approximately 1 nm) were >100-fold more potent than 3,5,3'-triiodothyronine in initiating vesicle binding to actin fibers in vitro. Thyroxine-dependent vesicle binding was calcium-, magnesium-, and ATP-dependent, suggesting the participation of one or more myosin motors, presumably myosin V. Addition of the myosin V globular tail, lacking the actin-binding head, specifically blocked thyroid hormone-dependent vesicle binding, and direct binding of the myosin V tail to enzyme-containing endosomes was thyroxine-dependent. Progressive NH(2)-terminal deletion of the myosin V tail and domain-specific antibody inhibition studies revealed that the thyroxine-dependent vesicle-tethering domain was localized to the last 21 amino acids of the COOH terminus. These data show that myosin V is responsible for thyroid hormone-dependent binding of primary endosomes to the microfilaments and suggest that this motor mediates the actin-based endocytosis of the type II iodothyronine deiodinase.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10882730&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M004221200
dc.subjectActins; Adenosine Triphosphate; Affinity Labels; Amino Acid Sequence; Animals; Animals, Newborn; Astrocytes; Calmodulin-Binding Proteins; Endocytosis; Endosomes; Immunohistochemistry; Iodide Peroxidase; Microfilaments; Molecular Motor Proteins; Molecular Sequence Data; Mutation; *Myosin Type V; Nerve Tissue Proteins; Protein Binding; Rats; Recombinant Fusion Proteins; Thyroid Hormones; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleMyosin V plays an essential role in the thyroid hormone-dependent endocytosis of type II iodothyronine 5'-deiodinase
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume275
dc.source.issue41
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1158
dc.identifier.contextkey693064
html.description.abstract<p>In astrocytes, thyroxine modulates type II iodothyronine 5'-deiodinase levels by initiating the binding of the endosomes containing the enzyme to microfilaments, followed by actin-based endocytosis. Myosin V is a molecular motor thought to participate in vesicle trafficking in the brain. In this report, we developed an in vitro actin-binding assay to characterize the thyroid hormone-dependent binding of endocytotic vesicles to microfilaments. Thyroxine and reverse triiodothyronine (EC(50) levels approximately 1 nm) were >100-fold more potent than 3,5,3'-triiodothyronine in initiating vesicle binding to actin fibers in vitro. Thyroxine-dependent vesicle binding was calcium-, magnesium-, and ATP-dependent, suggesting the participation of one or more myosin motors, presumably myosin V. Addition of the myosin V globular tail, lacking the actin-binding head, specifically blocked thyroid hormone-dependent vesicle binding, and direct binding of the myosin V tail to enzyme-containing endosomes was thyroxine-dependent. Progressive NH(2)-terminal deletion of the myosin V tail and domain-specific antibody inhibition studies revealed that the thyroxine-dependent vesicle-tethering domain was localized to the last 21 amino acids of the COOH terminus. These data show that myosin V is responsible for thyroid hormone-dependent binding of primary endosomes to the microfilaments and suggest that this motor mediates the actin-based endocytosis of the type II iodothyronine deiodinase.</p>
dc.identifier.submissionpathgsbs_sp/1158
dc.contributor.departmentDepartment of Physiology
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.contributor.departmentDepartment of Cellular and Molecular Physiology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages31701-7


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