TY - JOUR
T1 - Numb is an endocytic protein
AU - Santolini, Elisa
AU - Puri, Claudia
AU - Salcini, Anna Elisabetta
AU - Gagliani, Maria Cristina
AU - Pelicci, Pier Giuseppe
AU - Tacchetti, Carlo
AU - Di Fiore, Pier Paolo
PY - 2000/12/11
Y1 - 2000/12/11
N2 - 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.
AB - 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.
KW - EGFR
KW - EH domain
KW - Endocytosis
KW - Eps15
KW - Numb
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UR - http://www.scopus.com/inward/citedby.url?scp=0034638843&partnerID=8YFLogxK
U2 - 10.1083/jcb.151.6.1345
DO - 10.1083/jcb.151.6.1345
M3 - Article
C2 - 11121447
AN - SCOPUS:0034638843
VL - 151
SP - 1345
EP - 1351
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -