Differential effects of antimycin A on endocytosis and exocytosis of transferrin also are observed for internalization and externalization of beta-adrenergic receptors.
In many cells catecholamines induce a translocation of beta-adrenergic receptors from the cell surface to intracellular vesicular sites. We have postulated that the translocation event is the result of ligand-induced endocytosis of the receptor, probably via clathrin-coated pits. Previously, we demonstrated that reduction of cellular ATP content with antimycin A completely blocked endocytosis of epidermal growth factor and translocation of beta-adrenergic receptors in 1321N1 astrocytoma cells. However, the effect of reduction in ATP content on endocytosis remains controversial. In the present report, we demonstrate that reduction of ATP content to a level < 5% of that in control cells is sufficient to prevent endocytosis of [125I]iodotransferrin and translocation of beta-adrenergic receptors. The further demonstration that reactions leading to the return of internalized transferrin or beta-adrenergic receptors to the cell surface are blocked after relatively modest reductions in ATP content provides further evidence of the similarity in the processes subserving diacytosis of beta-adrenergic receptors and transferrin. The differential requirement for ATP of the two arms of diacytosis provides the basis for an explanation of the controversy regarding a requirement for ATP in endocytosis via clathrin-coated pits.
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
J F
JF
Liao
J P
JP
Perkins
D000255:Adenosine Triphosphate / Q000378:metabolism; D000968:Antimycin A / Q000494:pharmacology*; D001254:Astrocytoma; D002966:Clathrin / Q000737:chemistry; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects*; D005089:Exocytosis / Q000187:drug effects*; D006801:Humans; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002966:Clathrin; D011943:Receptors, Adrenergic, beta; D011990:Receptors, Transferrin; D014168:Transferrin; D000968:Antimycin A; D000255:Adenosine Triphosphate