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Numb Is an Endocytic Protein

Numb Is an Endocytic Protein Numb is a protein that in Drosophila determines cell fate as a result of its asymmetric partitioning at mitosis. The function of Numb has been linked to its ability to bind and to biologically antagonize Notch, a membrane receptor that also specifies cell fate. The biochemical mechanisms underlying the action of Numb, however, are still largely unknown. The wide pattern of expression of Numb suggests a general function in cellular homeostasis that could be additional to, or part of, its action in fate determination. Such a function could be endocytosis, as suggested by the interaction of Numb with Eps15, a component of the endocytic machinery. Here, we demonstrate that Numb is an endocytic protein. We found that Numb localizes to endocytic organelles and is cotrafficked with internalizing receptors. Moreover, it associates with the appendage domain of α adaptin, a subunit of AP2, a major component of clathrin-coated pits. Finally, fragments of Numb act as dominant negatives on both constitutive and ligand-regulated receptor-mediated internalization, suggesting a general role for Numb in the endocytic process. Numb endocytosis EH domain EGFR Eps15 Footnotes Abbreviations used in this paper: aa, amino acid(s); dNumb, Drosophila Numb; DPF, Asp-Pro-Phe; DLA, Asp-Leu-Ala; EH, Eps15 homology; GST, glutathione S -transferase; HA, hemagglutinin; NPF, Asn-Pro-Phe; mNumb, mammalian Numb; Tf, transferrin; TfR; Tf receptor. Submitted: 7 August 2000 Revision requested 11 October 2000 Accepted: 16 October 2000 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Cell Biology Rockefeller University Press

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Publisher
Rockefeller University Press
Copyright
© 2000 The Rockefeller University Press
ISSN
0021-9525
eISSN
1540-8140
DOI
10.1083/jcb.151.6.1345
Publisher site
See Article on Publisher Site

Abstract

Numb is a protein that in Drosophila determines cell fate as a result of its asymmetric partitioning at mitosis. The function of Numb has been linked to its ability to bind and to biologically antagonize Notch, a membrane receptor that also specifies cell fate. The biochemical mechanisms underlying the action of Numb, however, are still largely unknown. The wide pattern of expression of Numb suggests a general function in cellular homeostasis that could be additional to, or part of, its action in fate determination. Such a function could be endocytosis, as suggested by the interaction of Numb with Eps15, a component of the endocytic machinery. Here, we demonstrate that Numb is an endocytic protein. We found that Numb localizes to endocytic organelles and is cotrafficked with internalizing receptors. Moreover, it associates with the appendage domain of α adaptin, a subunit of AP2, a major component of clathrin-coated pits. Finally, fragments of Numb act as dominant negatives on both constitutive and ligand-regulated receptor-mediated internalization, suggesting a general role for Numb in the endocytic process. Numb endocytosis EH domain EGFR Eps15 Footnotes Abbreviations used in this paper: aa, amino acid(s); dNumb, Drosophila Numb; DPF, Asp-Pro-Phe; DLA, Asp-Leu-Ala; EH, Eps15 homology; GST, glutathione S -transferase; HA, hemagglutinin; NPF, Asn-Pro-Phe; mNumb, mammalian Numb; Tf, transferrin; TfR; Tf receptor. Submitted: 7 August 2000 Revision requested 11 October 2000 Accepted: 16 October 2000

Journal

The Journal of Cell BiologyRockefeller University Press

Published: Dec 11, 2000

References