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Vol. 16, Issue 8, 3480-3487, August 2005

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Regulation of Membrane Localization of Sanpodo by lethal giant larvae and neuralized in Asymmetrically Dividing Cells of Drosophila Sensory Organs

Howard Hughes Medical Institute and Department of Physiology and Biochemistry, University of California–San Francisco, San Francisco, CA 94143-0725

Submitted March 1, 2005; Revised April 15, 2005; Accepted May 11, 2005
Monitoring Editor: Susan Strome

In Drosophila, asymmetric division occurs during proliferation of neural precursors of the central and peripheral nervous system (PNS), where a membrane-associated protein, Numb, is asymmetrically localized during cell division and is segregated to one of the two daughter cells (the pIIb cell) after mitosis. numb has been shown genetically to function as an antagonist of Notch signaling and also as a negative regulator of the membrane localization of Sanpodo, a four-pass transmembrane protein required for Notch signaling during asymmetric cell division in the CNS. Previously, we identified lethal giant larvae (lgl) as a gene required for numb-mediated inhibition of Notch in the adult PNS. In this study we show that Sanpodo is expressed in asymmetrically dividing precursor cells of the PNS and that Sanpodo internalization in the pIIb cell is dependent cytoskeletally associated Lgl. Lgl specifically regulates internalization of Sanpodo, likely through endocytosis, but is not required for the endocytosis Delta, which is a required step in the Notch-mediated cell fate decision during asymmetric cell division. Conversely, the E3 ubiquitin ligase neuralized is required for both Delta endocytosis and the internalization of Sanpodo. This study identifies a hitherto unreported role for Lgl as a regulator of Sanpodo during asymmetric cell division in the adult PNS.

Abbreviations used: APF, after pupae formation; ES, external sensory; GFP, green fluorescent protein; Lgl, lethal giant larvae; MARCM, mosaic analysis with a repressible cell marker; Pon, partner of Numb; PNS, peripheral nervous system.

^* Present address: Institute for Cancer Research, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111.

Address correspondence to: Fabrice Roegiers (fabrice.roegiers{at}fccc.edu).