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 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.
Santolini
E
E
Department of Experimental Oncology, European Institute of Oncology, 20141 Milan, Italy.
Puri
C
C
Salcini
A E
AE
Gagliani
M C
MC
Pelicci
P G
PG
Tacchetti
C
C
Di Fiore
P P
PP
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D002451:Cell Compartmentation; D029721:Drosophila Proteins; D004705:Endocytosis / Q000235:genetics; D019084:Fluorescent Antibody Technique, Indirect; D006133:Growth Substances / Q000494:pharmacology; D019476:Insect Proteins / Q000378:metabolism; D007605:Juvenile Hormones / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D015388:Organelles / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins; D011485:Protein Binding
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; C094318:Eps15-rs protein, mouse; D006133:Growth Substances; D019476:Insect Proteins; D007605:Juvenile Hormones; D008565:Membrane Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; C060606:numb protein, Drosophila