Myosin V plays an essential role in the thyroid hormone-dependent endocytosis of type II iodothyronine 5'-deiodinase

J Biol Chem. 2000 Oct 13;275(41):31701-7. doi: 10.1074/jbc.M004221200.


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.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism
  • Actins / metabolism
  • Adenosine Triphosphate / metabolism
  • Affinity Labels
  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Calmodulin-Binding Proteins / chemistry
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Endocytosis / drug effects*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • Immunohistochemistry
  • Iodide Peroxidase / classification
  • Iodide Peroxidase / immunology
  • Iodide Peroxidase / metabolism*
  • Molecular Motor Proteins / chemistry
  • Molecular Motor Proteins / genetics
  • Molecular Motor Proteins / metabolism
  • Molecular Sequence Data
  • Mutation
  • Myosin Type V*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding / drug effects
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Thyroid Hormones / pharmacology*
  • Thyroxine / pharmacology
  • Triiodothyronine / pharmacology
  • Triiodothyronine, Reverse / pharmacology


  • Actins
  • Affinity Labels
  • Calmodulin-Binding Proteins
  • Molecular Motor Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • Thyroid Hormones
  • chicken brain myosin-V p190
  • Triiodothyronine
  • Triiodothyronine, Reverse
  • Adenosine Triphosphate
  • Iodide Peroxidase
  • Myosin Type V
  • Thyroxine