|Citation||Tong, X., Zitserman, D., Serebriiskii, I., Andrake, M., Dunbrack, R., Roegiers, F. (2010). Numb independently antagonizes sanpodo membrane targeting and notch signaling in Drosophila sensory organ precursor cells. Mol. Biol. Cell 21(5): 802--810. (Export to RIS)|
|Publication Type||Research paper|
|PubMed Abstract||In Drosophila, mitotic neural progenitor cells asymmetrically segregate the cell fate determinant Numb in order to block Notch signaling in only one of the two daughter cells. Sanpodo, a membrane protein required for Notch signaling in asymmetrically dividing cells, is sequestered from the plasma membrane to intracellular vesicles in a Numb-dependent way after neural progenitor cell mitosis. However, the significance of Numb-dependent Sanpodo regulation is unclear. In this study, we conducted a structure-function analysis to identify the determinants of Sanpodo targeting in vivo. We identified an NPAF motif in the amino-terminal cytoplasmic tail of Sanpodo, which is conserved among insect Sanpodo homologues. The Sanpodo NPAF motif is predicted to bind directly to the Numb phosphotyrosine-binding domain and is critical for Numb binding in vitro. Deletion or mutation of the NPAF motif results in accumulation of Sanpodo at the plasma membrane in Numb-positive cells in vivo. Genetic analysis of Sanpodo NPAF mutants shows that Numb-dependent Sanpodo endocytic targeting can be uncoupled from Notch signaling regulation. Our findings demonstrate that Sanpodo contains an evolutionarily conserved motif that has been linked to Numb-dependent regulation in vertebrates and further support the model that Numb regulates Notch signaling independently of Sanpodo membrane trafficking in neural progenitor cells.|
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|Language of Publication||English|
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|Also Published As|
|Abbreviation||Mol. Biol. Cell|
|Title||Molecular Biology of the Cell|
|Data from Reference|
|Natural transposons (1)|