Myosin V Plays an Essential Role in the Thyroid Hormone-dependent Endocytosis of Type II Iodothyronine 5′-Deiodinase

We developed an in vitro actin-binding assay to characterize the thyroid hormonedependent binding of endocytotic vesicles to microfilaments

Stanley J. Stachelek; Tim F. Kowalik; Alan P. Farwell; Jack L. Leonard

2002

Scholarcy highlights

  • Type II iodothyronine deiodinase1 is a membrane-bound enzyme that catalyzes the generation of T3 from T4, and is the major source of T3 in brain, pituitary, and brown adipose tissue
  • Preincubation of the anti-myosin V antibody with excess blocking peptide eliminated the 190-kDa immunoreactive band, indicating that the myosin V present in astrocytes is predominantly associated with the filamentous actin cytoskeleton
  • These data illustrate that, as reported previously, the retinoid-treated, thyroid hormone-deficient astrocyte contained a fully polymerized actin cytoskeleton and indicate that myosin V is constitutively bound to F-actin
  • In this study we show that a vesicle-tethering domain located at the COOH terminus of the unconventional myosin motor protein, myosin V, mediates the thyroid hormone-dependent attachment of endosomes to F-actin
  • The participation of myosin V in vesicle trafficking is well known. This motor protein has been shown to move vesicles along actin fibers in vitro, and loss of myosin V in yeast and in mice leads to profound defects in cell migration, vesicle trafficking, and oriented organelle transport
  • The ability of myosin V to dock with intracellular vesicles and tether these organelles to actin filaments is central to the function of this motor protein and to the ability of myosin V to participate in the thyroid hormone-dependent endocytosis of D2 in brain
  • The microtubule motor kinesin mediates axonal translocation of myosin V and its associated vesicles to the nerve terminal , the dynamic, T4-dependent regulation of D2 does not require intact microtubules, indicating that this is solely an actin-based endocytotic event

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