Endocytosis-independent mechanisms of Delta ligand proteolysis》.pdfVIP

E X P E R I M E N T A L C E L L R E S E A R C H 3 1 2 ( 2 0 0 6 ) 1 3 4 5 – 1 3 6 0 ava i l a b l e a t w w w. s c i e n c e d i r e c t . c o m w w w. e l s ev i e r. c o m / l o c a t e / yexc r Research Article Endocytosis-independent mechanisms of Delta ligand proteolysis Anton Delwig, Christin Bland, Micah Beem-Miller, Priscilla Kimberly, Matthew D. Rand⁎ Department of Anatomy and Neurobiology, HSRF 426C, College of Medicine, University of Vermont, Burlington, VT 05405, USA A R T I C L E I N F O R M A T I O N A B S T R A C T Article Chronology: Delta proteins function as cell surface ligands for Notch receptors in a highly conserved Received 20 October 2005 signal transduction mechanism. Delta activates Notch by “trans-endocytosis”, whereby Revised version received endocytosis of Delta that is in complex with Notch on a neighboring cell induces activating 21 December 2005 cleavages in Notch. Alternatively, proteolysis of Delta renders the ligand inactive by Accepted 24 December 2005 dissociating the extracellular and cytosolic domains. How proteolysis and trans-endocytosis Available online 17 February 2006 cooperate in Delta function is not well understood. We now show that Drosophila Delta proteolysis occurs independent of and prior to endocytosis in neuroblasts and ganglion Keywords: mother cells in vivo and cells in culture. Delta cleavage occurs at two novel sites that we Delta