dEHBP1 controls exocytosis and recycling of Delta during asymmetric divisions

J Cell Biol. 2012 Jan 9;196(1):65-83. doi: 10.1083/jcb.201106088. Epub 2012 Jan 2.

Abstract

Notch signaling governs binary cell fate determination in asymmetrically dividing cells. Through a forward genetic screen we identified the fly homologue of Eps15 homology domain containing protein-binding protein 1 (dEHBP1) as a novel regulator of Notch signaling in asymmetrically dividing cells. dEHBP1 is enriched basally and at the actin-rich interface of pII cells of the external mechanosensory organs, where Notch signaling occurs. Loss of function of dEHBP1 leads to up-regulation of Sanpodo, a regulator of Notch signaling, and aberrant trafficking of the Notch ligand, Delta. Furthermore, Sec15 and Rab11, which have been previously shown to regulate the localization of Delta, physically interact with dEHBP1. We propose that dEHBP1 functions as an adaptor molecule for the exocytosis and recycling of Delta, thereby affecting cell fate decisions in asymmetrically dividing cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Asymmetric Cell Division / physiology*
  • Drosophila / cytology*
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Exocytosis / physiology*
  • Gene Expression Regulation
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / metabolism
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Vesicular Transport Proteins / metabolism
  • rab GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Drosophila Proteins
  • EHD protein-binding protein 1, Drosophila
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • Receptors, Notch
  • Sec15 protein, Drosophila
  • Vesicular Transport Proteins
  • delta protein
  • spdo protein, Drosophila
  • Rab11 protein, Drosophila
  • rab GTP-Binding Proteins