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Numb inhibits the recycling of Sanpodo in Drosophila sensory organ precursor.

Abstract : In metazoans, unequal partitioning of the cell-fate determinant Numb underlies the generation of distinct cell fates following asymmetric cell division [1-5]. In Drosophila, during asymmetric division of the sensory organ precursor (SOP) cell, Numb is unequally inherited by the pIIb daughter cell, where it antagonizes Notch [1, 6-8]. Numb inhibits Notch partly through inhibiting the plasma membrane localization of Sanpodo (Spdo), a transmembrane protein required for Notch signaling during asymmetric cell division [9, 10]. Numb, by binding to Spdo and α-Adaptin, was proposed to mediate Spdo endocytosis alone or bound to Notch in the pIIb cell, thereby preventing Notch activation [11-16]. However, in addition to endocytosis, Numb also controls the postendocytic trafficking and degradation of Notch in mammals [17, 18] and negatively regulates basolateral recycling in C. elegans [19, 20]. Thus, whether Numb promotes the endocytosis of Spdo is a question that requires experimental demonstration and is therefore investigated in this article. Based on internalization assays, we show that Spdo endocytosis is restricted to cells in interphase and requires AP-2 activity. Surprisingly, the bulk endocytosis of Spdo occurs properly in numb mutant SOP, indicating that Numb does not regulate the steady-state localization of Spdo via Spdo internalization. We report that Numb genetically and physically interacts with AP-1, a complex regulating the basolateral recycling of Spdo [21]. In numb mutant organs, Spdo is efficiently internalized and recycled back to the plasma membrane. We propose that Numb acts in concert with AP-1 to control the endocytic recycling of Spdo to regulate binary-fate decisions.
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Contributor : Clémence Martin Connect in order to contact the contributor
Submitted on : Monday, May 27, 2013 - 12:02:28 PM
Last modification on : Wednesday, March 30, 2022 - 2:35:19 PM

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Mathieu Cotton, Najate Benhra, Roland Le Borgne. Numb inhibits the recycling of Sanpodo in Drosophila sensory organ precursor.. Current Biology - CB, Elsevier, 2013, 23 (7), pp.581-7. ⟨10.1016/j.cub.2013.02.020⟩. ⟨inserm-00826290⟩



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