Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP)

Hua Poo Su, Kumiko Nakada-Tsukui, Annie Carole Tosello-Trampont, Yonghe Li, Guojun Bu, Peter M. Henson, Kodimangalam S. Ravichandran

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

The prompt clearance of cells undergoing apoptosis is critical during embroyonic development, normal tissue turnover, as well as inflammation and autoimmunity. The molecular details of the engulfment of apoptotic cells are not fully understood. ced-6 and its human homologue gulf, encode an adapter protein, whose function in engulfment is highly evolutionarily conserved; however, the upstream and downstream components of CED-6 mediated signaling are not known. Recently, ced-1 has been shown to encode a transmembrane protein on phagocytic cells, with two functional sequence motifs in its cytoplasmic tail that are important for engulfment. In this study, using a combination of biochemical approaches and yeast two-hybrid analysis, we present evidence for a physical interaction between GULF/ CED-6 and one of the two motifs (NPXY motif) in the cytoplasmic tail of CED-1. The phosphotyrosine binding domain of GULF was necessary and sufficient for this interaction. Since the precise mammalian homologue of CED-1 is not known, we undertook a database search for humans proteins that contain the motifs shown to be important for CED-1 function and identified CD91/LRP (low density lipoprotein receptor-related protein) as one candidate. Interestingly, recent studies have also identified CD91/LRP as a receptor involved in the phagocytosis of apoptopic cells in mammals. The GULP phosphotyrosine binding domain was able to specifically interact with one specific NPXY motif in the CD91 cytoplasmic tail. During these studies we have also identified the mouse GULP sequences. These studies suggest a physical linkbetween CED-1 or CD91/LRP and the adapter protein CED-6/GULP during engulfment of apoptopic cells and further elucidate the pathway suggested by the genetic studies.

Original languageEnglish (US)
Pages (from-to)11772-11779
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number14
DOIs
StatePublished - Apr 5 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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