A Phosphatidylinositol 4,5-bisphosphate Redistribution-based Sensing Mechanism Initiates a Phagocytosis Programing

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Oct 17

PMID 30323235

Citations 27

Authors

Libing Mu

Zhongyuan Tu

Lin Miao

Hefei Ruan

Ning Kang

Yongzhen Hei

Jiahuan Chen

Wei Wei

Fangling Gong

Bingjie Wang

Yanan Du

Guanghui Ma

Matthias W Amerein

Tie Xia

Yan Shi

Affiliations

Soon will be listed here.

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.

Citing Articles

The Effects of Viral Structural Proteins on Acidic Phospholipids in Host Membranes.

de Souza Cardoso R, Ono A Viruses. 2024; 16(11).

PMID: 39599829 PMC: 11599007. DOI: 10.3390/v16111714.

Clec12a inhibits MSU-induced immune activation through lipid raft expulsion.

Xu Y, Song D, Wang W, Li S, Yue T, Xia T Life Sci Alliance. 2023; 6(9).

PMID: 37339805 PMC: 10282328. DOI: 10.26508/lsa.202301938.

Rab11a Is Essential for the Development and Integrity of the Stereocilia and Kinocilia in the Mammalian Organ of Corti.

Knapp L, Sun H, Wang Y, Chen B, Lin X, Gao N eNeuro. 2023; 10(6).

PMID: 37225424 PMC: 10249950. DOI: 10.1523/ENEURO.0420-22.2023.

Immunology of a unique biological structure: the Echinococcus laminated layer.

Diaz A, Barrios A, Grezzi L, Mouhape C, Jenkins S, Allen J Protein Cell. 2023; 14(2):87-104.

PMID: 36929004 PMC: 10019577. DOI: 10.1093/procel/pwac023.

Localisation of Intracellular Signals and Responses during Phagocytosis.

Hallett M Int J Mol Sci. 2023; 24(3).

PMID: 36769146 PMC: 9917157. DOI: 10.3390/ijms24032825.

References

Stuart L, Ezekowitz R . Phagocytosis and comparative innate immunity: learning on the fly. Nat Rev Immunol. 2008; 8(2):131-41. DOI: 10.1038/nri2240. View

Johnson C, Rodgers W . Spatial Segregation of Phosphatidylinositol 4,5-Bisphosphate (PIP(2)) Signaling in Immune Cell Functions. Immunol Endocr Metab Agents Med Chem. 2009; 8(4):349-357. PMC: 2771939. DOI: 10.2174/187152208787169233. View

Tauber A . Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol. 2003; 4(11):897-901. DOI: 10.1038/nrm1244. View

Kaufmann S . Immunology's foundation: the 100-year anniversary of the Nobel Prize to Paul Ehrlich and Elie Metchnikoff. Nat Immunol. 2008; 9(7):705-12. DOI: 10.1038/ni0708-705. View

Wells R . The role of matrix stiffness in regulating cell behavior. Hepatology. 2008; 47(4):1394-400. DOI: 10.1002/hep.22193. View

Taglieri D, Delfin D, Monasky M . Cholesterol regulation of PIP(2): why cell type is so important. Front Physiol. 2013; 3:492. PMC: 3539649. DOI: 10.3389/fphys.2012.00492. View

Kim H, Choo H, Jung S, Ko Y, Park W, Jeon S . A two-photon fluorescent probe for lipid raft imaging: C-laurdan. Chembiochem. 2007; 8(5):553-9. DOI: 10.1002/cbic.200700003. View

Bohdanowicz M, Grinstein S . Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis. Physiol Rev. 2013; 93(1):69-106. DOI: 10.1152/physrev.00002.2012. View

Hedges S, Marin J, Suleski M, Paymer M, Kumar S . Tree of life reveals clock-like speciation and diversification. Mol Biol Evol. 2015; 32(4):835-45. PMC: 4379413. DOI: 10.1093/molbev/msv037. View

10.

Bretscher A, Edwards K, Fehon R . ERM proteins and merlin: integrators at the cell cortex. Nat Rev Mol Cell Biol. 2002; 3(8):586-99. DOI: 10.1038/nrm882. View

11.

Bowdish D, Gordon S . Conserved domains of the class A scavenger receptors: evolution and function. Immunol Rev. 2009; 227(1):19-31. DOI: 10.1111/j.1600-065X.2008.00728.x. View

12.

Gauthier N, Masters T, Sheetz M . Mechanical feedback between membrane tension and dynamics. Trends Cell Biol. 2012; 22(10):527-35. DOI: 10.1016/j.tcb.2012.07.005. View

13.

Sundstrom G, Larsson T, Brenner S, Venkatesh B, Larhammar D . Evolution of the neuropeptide Y family: new genes by chromosome duplications in early vertebrates and in teleost fishes. Gen Comp Endocrinol. 2007; 155(3):705-16. DOI: 10.1016/j.ygcen.2007.08.016. View

14.

Dustin M . Complement Receptors in Myeloid Cell Adhesion and Phagocytosis. Microbiol Spectr. 2016; 4(6). PMC: 5580235. DOI: 10.1128/microbiolspec.MCHD-0034-2016. View

15.

Ng G, Sharma K, Ward S, Desrosiers M, Stephens L, Schoel W . Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells. Immunity. 2008; 29(5):807-18. PMC: 2642965. DOI: 10.1016/j.immuni.2008.09.013. View

16.

Carvalho K, Ramos L, Roy C, Picart C . Giant unilamellar vesicles containing phosphatidylinositol(4,5)bisphosphate: characterization and functionality. Biophys J. 2008; 95(9):4348-60. PMC: 2567945. DOI: 10.1529/biophysj.107.126912. View

17.

Machnicka B, Czogalla A, Hryniewicz-Jankowska A, Boguslawska D, Grochowalska R, Heger E . Spectrins: a structural platform for stabilization and activation of membrane channels, receptors and transporters. Biochim Biophys Acta. 2013; 1838(2):620-34. DOI: 10.1016/j.bbamem.2013.05.002. View

18.

Golovnina K, Blinov A, Akhmametyeva E, Omelyanchuk L, Chang L . Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene. BMC Evol Biol. 2005; 5:69. PMC: 1315344. DOI: 10.1186/1471-2148-5-69. View

19.

Bolen J, Thompson P, Eiseman E, Horak I . Expression and interactions of the Src family of tyrosine protein kinases in T lymphocytes. Adv Cancer Res. 1991; 57:103-49. DOI: 10.1016/s0065-230x(08)60997-5. View

20.

Chierico L, Joseph A, Lewis A, Battaglia G . Live cell imaging of membrane/cytoskeleton interactions and membrane topology. Sci Rep. 2014; 4:6056. PMC: 4159633. DOI: 10.1038/srep06056. View