Endothelin-induced endocytosis of cell surface ETA receptors. Endothelin remains intact and bound to the ETA receptor.
We demonstrate unusual features of the intracellular processing of endothelin-1 (ET-1) and its receptor ETA, the receptor subtype that mediates contraction of vascular smooth muscle cells. First, we show that in stably transfected CHO cells expressing ETA, binding of an ET-1 ligand induces rapid endocytosis of cell surface ETA. Receptor endocytosis was measured both by immunofluorescence and by radioiodinated antibodies specific for ETA. Second, we demonstrate that ET-1 remains intact for up to 2 h after endocytosis and, as judged by co-immunoprecipitation, internalized 125I-ET-1 remains bound to ETA receptors. We hypothesize that internalized ET-1, bound to ETA receptors, continues to activate a signal-transducing G protein, thus accounting for the prolonged period of contraction induced in smooth muscle cells by a single administration of ET-1.
Chun
M
M
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.
Lin
H Y
HY
Henis
Y I
YI
Lodish
H F
HF
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004705:Endocytosis; D016232:Endothelins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism*; D013997:Time Factors
D016232:Endothelins; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D019204:GTP-Binding Proteins