CAS OpenIR
A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing
Mu, Libing1,2,3,4; Tu, Zhongyuan5,6; Miao, Lin2,3,4,7; Ruan, Hefei1,2,3,4; Kang, Ning1,2,3,4; Hei, Yongzhen2,3,4; Chen, Jiahuan1,2,3,4; Wei, Wei8; Gong, Fangling8; Wang, Bingjie9; Du, Yanan9; Ma, Guanghui8; Amerein, Matthias W.10,11; Xia, Tie1,2,3,4; Shi, Yan1,2,3,4,5,6
2018-10-15
Source PublicationNATURE COMMUNICATIONS
ISSN2041-1723
Volume9Pages:16
Abstract

Phagocytosis is one of the earliest cellular functions, developing approximately 2 billion years ago. Although FcR-based phagocytic signaling is well-studied, how it originated from ancient phagocytosis is unknown. Lipid redistribution upregulates a phagocytic program recapitulating FcR-based phagocytosis with complete dependence on Src family kinases, Syk, and phosphoinositide 3-kinases (PI3K). Here we show that in phagocytes, an atypical ITAM sequence in the ancient membrane anchor protein Moesin transduces signal without receptor activation. Plasma membrane deformation created by solid structure binding generates phosphatidylinositol 4,5-bisphosphate (PIP2) accumulation at the contact site, which binds the Moesin FERM domain and relocalizes Syk to the membrane via the ITAM motif. Phylogenic analysis traces this signaling using PI3K and Syk to 0.8 billion years ago, earlier than immune receptor signaling. The proposed general model of solid structure phagocytosis implies a preexisting lipid redistribution-based activation platform collecting intracellular signaling components for the emergence of immune receptors.

DOI10.1038/s41467-018-06744-7
Language英语
WOS KeywordGiant Unilamellar Vesicles ; Erm Proteins ; Plasma-membrane ; Divergence Times ; Ferm Domain ; Scavenger Receptors ; Actin Cytoskeleton ; Cell-adhesion ; Activation ; Binding
Funding Projectjoint Peking-Tsinghua Center for Life Sciences ; National Natural Science Foundation of China[31370878] ; State Key Program[31630023] ; Innovative Research Group Program[81621002] ; US NIH[R01AI098995] ; Canadian Institutes for Health Research[MOP-119295]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
Funding Organizationjoint Peking-Tsinghua Center for Life Sciences ; National Natural Science Foundation of China ; State Key Program ; Innovative Research Group Program ; US NIH ; Canadian Institutes for Health Research
WOS IDWOS:000447298400004
PublisherNATURE PUBLISHING GROUP
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/26151
Collection中国科学院过程工程研究所
Corresponding AuthorXia, Tie; Shi, Yan
Affiliation1.Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China
2.Tsinghua Univ, Inst Immunol, Sch Med, Beijing 100084, Peoples R China
3.Tsinghua Univ, Dept Basic Med Sci, Sch Med, Beijing Key Lab Immunol Res Chron Dis, Beijing 100084, Peoples R China
4.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China
5.Univ Calgary, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 4N1, Canada
6.Univ Calgary, Snyder Inst, Calgary, AB T2N 4N1, Canada
7.Peking Univ, Sch Life Sci, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
8.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
9.Tsinghua Univ, Sch Med, Dept Biomed Engn, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 100084, Peoples R China
10.Univ Calgary, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada
11.Univ Calgary, Snyder Inst Chron Dis, Calgary, AB T2N 4N1, Canada
Recommended Citation
GB/T 7714
Mu, Libing,Tu, Zhongyuan,Miao, Lin,et al. A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing[J]. NATURE COMMUNICATIONS,2018,9:16.
APA Mu, Libing.,Tu, Zhongyuan.,Miao, Lin.,Ruan, Hefei.,Kang, Ning.,...&Shi, Yan.(2018).A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing.NATURE COMMUNICATIONS,9,16.
MLA Mu, Libing,et al."A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing".NATURE COMMUNICATIONS 9(2018):16.
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