title: Reticulocalbin-1 facilitates microglial phagocytosis.
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.
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Life Sciences, University of Nevada Las Vegas, Las Vegas, NV, 89154, United States of America.
authors.forename: Nora B
authors.initials: NB
authors.lastname: Caberoy
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America.
authors.forename: Feiye
authors.initials: F
authors.lastname: Guo
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: LeBlanc
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America; Jinan 2nd People's Hospital, Jinan, 250001, China.
authors.forename: Chenming
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: Dept. of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, 77030, United States of America.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Dept. of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, 77030, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Bascom Palmer Eye Institute, Dept. of Ophthalmology, University of Miami School of Medicine, Miami, FL, 33136, United States of America; Neuroscience Program, University of Miami School of Medicine, Miami, FL, 33136, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008264:Macrophages / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010588:Phagosomes; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D002135:Calcium-Binding Proteins; D008024:Ligands; C078865:reticulocalbin