Numb is an endocytic protein

Elisa Santolini, Claudia Puri, Anna Elisabetta Salcini, Maria Cristina Gagliani, Pier Giuseppe Pelicci, Carlo Tacchetti, Pier Paolo Di Fiore

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1345-1351
Number of pages7
JournalJournal of Cell Biology
Volume151
Issue number6
DOIs
Publication statusPublished - Dec 11 2000

Keywords

  • EGFR
  • EH domain
  • Endocytosis
  • Eps15
  • Numb

ASJC Scopus subject areas

  • Cell Biology

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