Reference Report

Reference
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)
FlyBase ID	FBrf0210112
Publication Type	Research paper
PubMed ID	20053677
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.
DOI	10.1091/mbc.E09-09-0831
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Mol. Biol. Cell
Title	Molecular Biology of the Cell
Publication Year	1992-
ISBN/ISSN	1059-1524
Data from Reference
Alleles (18)
	AP-2α^ear4 l(2)gl⁴ Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} numb² numb^{fl.Scer\UAS.T:Hsap\MYC} Scer\GAL4^{neur-GAL4-A101} Scer\GAL4^sca-DB sec15² spdo^{1-424.Scer\UAS.T:Mmus\Cd8a,T:Avic\GFP-EGFP} spdo^C55 spdo^{NPAA.Scer\UAS.T:Avic\GFP-EGFP} spdo^{Scer\UAS.T:Avic\GFP-EGFP} spdo^{Δ1-180.Scer\UAS.T:Avic\GFP-EGFP} spdo^{Δ1-424.Scer\UAS.T:Avic\GFP-EGFP} spdo^{Δ196-255.Scer\UAS.T:Avic\GFP-EGFP} spdo^{Δ424-565.Scer\UAS.T:Avic\GFP-EGFP} spdo^{ΔN18.Scer\UAS.T:Avic\GFP-EGFP} T:Avic\GFP^EGFP
Constructs (10)
	P{UAS-mCD8::GFP.L} P{UAS-numb.T:Myc.Y} P{UAS-spdo.GFP} P{UAS-spdo.mCD8.1-424.GFP} P{UAS-spdo.NPAA.GFP} P{UAS-spdo.Δ1-180.GFP} P{UAS-spdo.Δ1-424.GFP} P{UAS-spdo.Δ196-255.GFP} P{UAS-spdo.Δ424-565.GFP} P{UAS-spdo.ΔN18.GFP}
Genes (12)
	AP-2α ct l(2)gl Mmus\Cd8a N numb Rab5 Scer\GAL4 sec15 spdo Su(H) T:Mmus\Cd8a
Insertions (2)
	P{GawB}neur^GAL4-A101 P{GawB}sca^DB
Natural transposons (1)
	P-element