Reticulocalbin-1 facilitates microglial phagocytosis

Ying Ding, Nora B. Caberoy, Feiye Guo, Michelle E. LeBlanc, Chenming Zhang, Weiwen Wang, Feng Wang, Rui Chen, Wei Li

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Phagocytosis is critical to the clearance of apoptotic cells, cellular debris and deleterious metabolic products for tissue homeostasis. Phagocytosis ligands directly recognizing deleterious cargos are the key to defining the functional roles of phagocytes, but are traditionally identified on a case-by-case basis with technical challenges. As a result, extrinsic regulation of phagocytosis is poorly defined. Here we demonstrate that microglial phagocytosis ligands can be systematically identified by a new approach of functional screening. One of the identified ligands is reticulocalbin-1 (Rcn1), which was originally reported as a Ca2+-binding protein with a strict expression in the endoplasmic reticulum. Our results showed that Rcn1 can be secreted from healthy cells and that secreted Rcn1 selectively bound to the surface of apoptotic neurons, but not healthy neurons. Independent characterization revealed that Rcn1 stimulated microglial phagocytosis of apoptotic but not healthy neurons. Ingested apoptotic cells were targeted to phagosomes and co-localized with phagosome marker Rab7. These data suggest that Rcn1 is a genuine phagocytosis ligand. The new approach described in this study will enable systematic identification of microglial phagocytosis ligands with broad applicability to many other phagocytes.

Original languageEnglish (US)
Article numbere0126993
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Ding, Y., Caberoy, N. B., Guo, F., LeBlanc, M. E., Zhang, C., Wang, W., Wang, F., Chen, R., & Li, W. (2015). Reticulocalbin-1 facilitates microglial phagocytosis. PloS one, 10(5), [e0126993]. https://doi.org/10.1371/journal.pone.0126993