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Published online 11 December 2000. doi:10.1083/jcb.151.6.1345
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© The Rockefeller University Press, 0021-9525/2000//1345 $5.00
The Journal of Cell Biology, Volume 151, Number 6, , 2000 1345-1352

Report

Numb Is an Endocytic Protein



Elisa Santolinia, Claudia Purib, Anna Elisabetta Salcinia, Maria Cristina Gaglianib, Pier Giuseppe Peliccia,c, Carlo Tacchettib, and Pier Paolo Di Fiorea,c

a Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy
b Department of Experimental Medicine, Anatomy Section, University of Genova, 16132 Genova, Italy
c IFOM, The FIRC Institute for Molecular Oncology, 20134 Milan, Italy
Istituto Europeo di Oncologia, Via Ripamonti 435, 20141 Milan, Italy.39-02-5748985139-02-57489855

pdifiore{at}ieo.it

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 {alpha} 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.

Key Words: Numb • endocytosis • EH domain • EGFR • Eps15

© 2000 The Rockefeller University Press

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.


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