Editors' ChoiceReceptor Endocytosis

Endocytosis, Cleavage, and Signaling by Notch

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Science's STKE  14 Mar 2000:
Vol. 2000, Issue 23, pp. tw1
DOI: 10.1126/stke.2000.23.tw1

Notch and Delta are transmembrane proteins that interact as receptor and ligand. Signaling by Notch involves the cleavage of the intracellular domain, which acts with the primary Notch signal transducer Suppressor of Hairless to regulate transcription in Drosophila. Parks et al. found that signaling through Notch was dependent on endocytosis of Delta complexed with the Notch extracellular domain into the Delta-expressing cell. They analyzed the function and subcellular distribution of Delta and Notch intracellular and extracellular domains in flies with mutations in genes involved in endocytosis. Binding to Delta appeared not to be sufficient to initiate Notch cleavage and signaling, because mutations in Delta that disrupted endocytosis without affecting Notch binding were blocked in Delta-Notch signaling in the developing eye and wing vein. Thus, proper processing of Notch is dependent on both the binding and endocytosis of Delta.

Parks, A.L., Klueg, K.M., Stout, J.R, and Muskavitch, M.A.T. (2000) Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 127: 1373-1385. [Online Journal]

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