Ligand endocytosis drives receptor dissociation and activation in the Notch pathway (original) (raw)
RESEARCH ARTICLE| 01 April 2000
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Search for other works by this author on:
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Search for other works by this author on:
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Search for other works by this author on:
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Search for other works by this author on:
Annette L. Parks
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Kristin M. Klueg
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Jane R. Stout
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Marc A. T. Muskavitch*
Department of Biology
,
Indiana University
,
Bloomington, IN, 47405, USA
Present address: Exelixis Pharmaceuticals, Inc., 260 Littlefield Ave., South San Francisco, CA 94080, USA
Online ISSN: 1477-9129
Print ISSN: 0950-1991
© 2000 by Company of Biologists
2000
Development (2000) 127 (7): 1373–1385.
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ABSTRACT
Endocytosis of the ligand Delta is required for activation of the receptor Notch during Drosophila development. The Notch extracellular domain (NotchECD) dissociates from the Notch intracellular domain (NotchICD) and is trans-endocytosed into Delta-expressing cells in wild-type imaginal discs. Reduction of dynamin-mediated endocytosis in developing eye and wing imaginal discs reduces Notch dissociation and Notch signalling. Furthermore, dynamin-mediated Delta endocytosis is required for Notch trans_-_endocytosis in Drosophila cultured cell lines. Endocytosis-defective Delta proteins fail to mediate trans-endocytosis of Notch in cultured cells, and exhibit aberrant subcellular trafficking and reduced signalling capacity in Drosophila. We suggest that endocytosis into Delta-expressing cells of NotchECD bound to Delta plays a critical role during activation of the Notch receptor and is required to achieve processing and dissociation of the Notch protein.
© 2000 by Company of Biologists
2000
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