Myosin V plays an essential role in the thyroid hormone-dependent endocytosis of type II iodothyronine 5'-deiodinase
dc.contributor.author | Stachelek, Stanley J. | |
dc.contributor.author | Kowalik, Timothy F. | |
dc.contributor.author | Farwell, Alan P. | |
dc.contributor.author | Leonard, Jack L. | |
dc.date | 2022-08-11T08:08:48.000 | |
dc.date.accessioned | 2022-08-23T16:09:02Z | |
dc.date.available | 2022-08-23T16:09:02Z | |
dc.date.issued | 2000-07-07 | |
dc.date.submitted | 2009-01-13 | |
dc.identifier.citation | J 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.issn | 0021-9258 (Print) | |
dc.identifier.doi | 10.1074/jbc.M004221200 | |
dc.identifier.pmid | 10882730 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/32595 | |
dc.description.abstract | 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. | |
dc.language.iso | en_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.url | http://dx.doi.org/10.1074/jbc.M004221200 | |
dc.subject | Actins; 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.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Myosin V plays an essential role in the thyroid hormone-dependent endocytosis of type II iodothyronine 5'-deiodinase | |
dc.type | Journal Article | |
dc.source.journaltitle | The Journal of biological chemistry | |
dc.source.volume | 275 | |
dc.source.issue | 41 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/1158 | |
dc.identifier.contextkey | 693064 | |
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.submissionpath | gsbs_sp/1158 | |
dc.contributor.department | Department of Physiology | |
dc.contributor.department | Department of Molecular Genetics and Microbiology | |
dc.contributor.department | Department of Cellular and Molecular Physiology | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 31701-7 |