In the brain, thyroid hormone dynamically regulates levels of the short-lived 
plasma membrane protein, type II iodothyronine 5'-deiodinase. In cultured 
astrocytes, thyroxine modulates deiodinase levels by activating 
cytoskeletal-plasma membrane interactions that increase the rate of inactivation 
of the enzyme. Here we characterized the effects of these thyroxine-dependent 
cytoskeletal interactions upon the route of internalization of the deiodinase by 
following the intracellular transit of the affinity-labeled substrate-binding 
subunit of the deiodinase (p29). Thyroxine rapidly induced the inactivation of 
the deiodinase and initiated the binding of p29 to F-actin. By 40 min, > 75% of 
the p29 had been transported to an endosomal pool, which was followed by 
dissociation of the F-actin-p29 complex. There was no significant accumulation 
of p29 in the dense lysosomes seen in the presence of thyroxine. In the absence 
of thyroxine, p29 was internalized and transported to the dense lysosomes at a 
rate parallel to the inactivation rate of the deiodinase (t1/2 0.75 and 0.64 h, 
respectively) without involvement with the microfilaments. These data 
demonstrate that thyroxine targets type II iodothyronine 5'-deiodinase to an 
endosomal pool by activating specific protein-F-actin interactions involved in 
microfilament-mediated intracellular protein trafficking.