Identification of tubby and tubby-like protein 1 as eat-me signals by phage display

Nora B. Caberoy, Dony Maiguel, Youngbae Kim, Wei Li

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Phagocytosis is an important process for the removal of apoptotic cells or cellular debris. Eat-me signals control the initiation of phagocytosis and hold the key for in-depth understanding of its molecular mechanisms. However, because of difficulties to identify unknown eat-me signals, only a limited number of them have been identified and characterized. Using a newly developed functional cloning strategy of open reading frame (ORF) phage display, we identified nine putative eat-me signals, including tubby-like protein 1 (Tulp1). This further led to the elucidation of tubby as the second eat-me signal in the same protein family. Both proteins stimulated phagocytosis of retinal pigment epithelium (RPE) cells and macrophages. Tubby-conjugated fluorescent microbeads facilitated RPE phagocytosis. Tubby and Tulp1, but not other family members, enhanced the uptake of membrane vesicles by RPE cells in synergy. Retinal membrane vesicles of Tubby mice and Tulp1-/- mice showed reduced activities for RPE phagocytosis, which were compensated by purified tubby and Tulp1, respectively. These data reveal a novel activity of tubby and Tulp1, and demonstrate that unbiased identification of eat-me signals by the broadly applicable strategy of ORF phage display can provide detailed insights into phagocyte biology.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalExperimental Cell Research
Volume316
Issue number2
DOIs
StatePublished - Jan 15 2010

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Bacteriophages
Phagocytosis
Retinal Pigment Epithelium
Proteins
Open Reading Frames
Membranes
Phagocytes
Microspheres
Organism Cloning
Macrophages

Keywords

  • Eat-me signal
  • Phage display
  • Phagocytosis
  • Retinal pigment epithelium
  • Tubby
  • Tulp1

ASJC Scopus subject areas

  • Cell Biology

Cite this

Identification of tubby and tubby-like protein 1 as eat-me signals by phage display. / Caberoy, Nora B.; Maiguel, Dony; Kim, Youngbae; Li, Wei.

In: Experimental Cell Research, Vol. 316, No. 2, 15.01.2010, p. 245-257.

Research output: Contribution to journalArticle

Caberoy, Nora B. ; Maiguel, Dony ; Kim, Youngbae ; Li, Wei. / Identification of tubby and tubby-like protein 1 as eat-me signals by phage display. In: Experimental Cell Research. 2010 ; Vol. 316, No. 2. pp. 245-257.
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