title: CD300b regulates the phagocytosis of apoptotic cells via phosphatidylserine recognition.
abstract: The CD300 receptor family members are a group of molecules that modulate a variety of immune cell processes. We show that mouse CD300b (CLM7/LMIR5), expressed on myeloid cells, recognizes outer membrane-exposed phosphatidylserine (PS) and does not, as previously reported, directly recognize TIM1 or TIM4. CD300b accumulates in phagocytic cups along with F-actin at apoptotic cell contacts, thereby facilitating their engulfment. The CD300b-mediated activation signal is conveyed through CD300b association with the adaptor molecule DAP12, and requires a functional DAP12 ITAM motif. Binding of apoptotic cells promotes the activation of the PI3K-Akt kinase pathway in macrophages, while silencing of CD300b expression diminishes PI3K-Akt kinase activation and impairs efferocytosis. Collectively, our data show that CD300b recognizes PS as a ligand, and regulates the phagocytosis of apoptotic cells via the DAP12 signaling pathway.
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: O H
authors.initials: OH
authors.lastname: Voss
authors.affiliation: Molecular Biology Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Margulies
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Krzewski
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Coligan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D051379:Mice; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527073:LMIR5 protein, mouse; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; C484963:Tyrobp protein, mouse; D019869:Phosphatidylinositol 3-Kinases