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 language | English (US) |
|---|---|
| Article number | e0126993 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 18 2015 |
Fingerprint
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Reticulocalbin-1 facilitates microglial phagocytosis. / Ding, Ying; Caberoy, Nora B.; Guo, Feiye; LeBlanc, Michelle E.; Zhang, Chenming; Wang, Weiwen; Wang, Feng; Chen, Rui; Li, Wei.
In: PLoS One, Vol. 10, No. 5, e0126993, 18.05.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reticulocalbin-1 facilitates microglial phagocytosis
AU - Ding, Ying
AU - Caberoy, Nora B.
AU - Guo, Feiye
AU - LeBlanc, Michelle E.
AU - Zhang, Chenming
AU - Wang, Weiwen
AU - Wang, Feng
AU - Chen, Rui
AU - Li, Wei
PY - 2015/5/18
Y1 - 2015/5/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930642697&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930642697&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0126993
DO - 10.1371/journal.pone.0126993
M3 - Article
C2 - 25992960
AN - SCOPUS:84930642697
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0126993
ER -