Galectin-3 is a new MerTK-specific eat-me signal

Nora B. Caberoy, Gabriela Alvarado, Jo Lawrence Bigcas, Wei Li

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Phagocytosis of apoptotic cells and cellular debris is a critical process of maintaining tissue and immune homeostasis. Defects in the phagocytosis process cause autoimmunity and degenerative diseases. Phagocytosis ligands or "eat-me" signals control the initiation of the process by linking apoptotic cells to receptors on phagocyte surface and triggering signaling cascades for cargo engulfment. Eat-me signals are traditionally identified on a case-by-case basis with challenges, and the identification of their cognate receptors is equally daunting. Here, we identified galectin-3 (Gal-3) as a new MerTK ligand by an advanced dual functional cloning strategy, in which phagocytosis-based functional cloning is combined with receptor-based affinity cloning to directly identify receptor-specific eat-me signal. Gal-3 interaction with MerTK was independently verified by co-immunoprecipitation. Functional analyses showed that Gal-3 stimulated the phagocytosis of apoptotic cells and cellular debris by macrophages and retinal pigment epithelial cells with MerTK activation and autophosphorylation. The Gal-3-mediated phagocytosis was blocked by excessive soluble MerTK extracellular domain and lactose. These results suggest that Gal-3 is a legitimate MerTK-specific eat-me signal. The strategy of dual functional cloning with applicability to other phagocytic receptors will facilitate unbiased identification of their unknown ligands and improve our capacity for therapeutic modulation of phagocytic activity and innate immune response.

Original languageEnglish
Pages (from-to)401-407
Number of pages7
JournalJournal of Cellular Physiology
Volume227
Issue number2
DOIs
StatePublished - Jan 1 2012

Fingerprint

Galectin 3
Cloning
Phagocytosis
Organism Cloning
Cytophagocytosis
Cells
Ligands
Debris
Retinal Pigments
Macrophages
Lactose
Phagocytes
Autoimmunity
Immunoprecipitation
Innate Immunity
Homeostasis
Epithelial Cells
Chemical activation
Modulation
Tissue

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Galectin-3 is a new MerTK-specific eat-me signal. / Caberoy, Nora B.; Alvarado, Gabriela; Bigcas, Jo Lawrence; Li, Wei.

In: Journal of Cellular Physiology, Vol. 227, No. 2, 01.01.2012, p. 401-407.

Research output: Contribution to journalArticle

Caberoy, Nora B. ; Alvarado, Gabriela ; Bigcas, Jo Lawrence ; Li, Wei. / Galectin-3 is a new MerTK-specific eat-me signal. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 2. pp. 401-407.
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