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Numb and α‐Adaptin regulate Sanpodo endocytosis to specify cell fate in Drosophila external sensory organs
Author(s) -
Hutterer Andrea,
Knoblich Juergen A
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400500
Subject(s) - numb , endocytosis , microbiology and biotechnology , endocytic cycle , biology , notch signaling pathway , cell fate determination , clathrin , mitosis , transmembrane protein , cell , signal transduction , receptor , genetics , gene , transcription factor
During asymmetric cell division in Drosophila sensory organ precursors (SOPs), the Numb protein segregates into one of the two daughter cells, in which it inhibits Notch signalling to specify pIIb cell fate. We show here that Numb acts in SOP cells by inducing the endocytosis of Sanpodo, a four‐pass transmembrane protein that has previously been shown to regulate Notch signalling in the central nervous system. In sanpodo mutants, SOP cells divide symmetrically into two pIIb cells. We show that Sanpodo is cortical in pIIa, but colocalizes with Notch and Delta in Rab5‐ and Rab7‐positive endocytic vesicles in pIIb. Sanpodo endocytosis requires α‐Adaptin, a Numb‐binding partner involved in clathrin‐mediated endocytosis. In numb or α‐ adaptin mutants, Sanpodo is not endocytosed. Surprisingly, this defect is observed already before and during mitosis, which suggests that Numb not only acts in pIIb, but also regulates endocytosis throughout the cell cycle. Numb binds to Sanpodo by means of its phosphotyrosine‐binding domain, a region that is essential for Numb function. Our results establish numb ‐ and α‐ adaptin ‐dependent endocytosis of Sanpodo as the mechanism by which Notch is regulated during external sensory organ development.