Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment

Chunguang Ren, Qianying Yuan, Martha Braun, Xia Zhang, Björn Petri, Jiasheng Zhang, Dongjoo Kim, Julia Guez-Haddad, Wenzhi Xue, Weijun Pan, Rong Fan, Paul Kubes, Zhaoxia Sun, Yarden Opatowsky, Franck Polleux, Erdem Karatekin, Wenwen Tang, Dianqing Wu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Cell polarization is important for various biological processes. However, its regulation, particularly initiation, is incompletely understood. Here, we investigated mechanisms by which neutrophils break their symmetry and initiate their cytoskeleton polarization from an apolar state in circulation for their extravasation during inflammation. We show here that a local increase in plasma membrane (PM) curvature resulting from cell contact to a surface triggers the initial breakage of the symmetry of an apolar neutrophil and is required for subsequent polarization events induced by chemical stimulation. This local increase in PM curvature recruits SRGAP2 via its F-BAR domain, which in turn activates PI4KA and results in PM PtdIns4P polarization. Polarized PM PtdIns4P is targeted by RPH3A, which directs PIP5K1C90 and subsequent phosphorylated myosin light chain polarization, and this polarization signaling axis regulates neutrophil firm attachment to endothelium. Thus, this study reveals a mechanism for the initiation of cell cytoskeleton polarization. The molecular mechanisms controlling cell polarization are incompletely understood. Ren and Yuan et al. show that local increase in plasma membrane (PM) curvature resulting from cell attachment recruits and polarizes an inverse FBAR domain protein SRGAP2 to initiate cell cytoskeleton polarization, which is important for neutrophil adhesion to endothelium.

Original languageEnglish
Pages (from-to)206-219.e7
JournalDevelopmental Cell
Volume49
Issue number2
DOIs
StatePublished - 22 Apr 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Inc.

Funding

We thank Michelle Orsulak for technical assistance, Pietro De Camilli for providing PIP5K1C antibody ( Di Paolo et al., 2002 ) and human PI4KA cDNA, Guangxin Li and George Tellides for the mT/mG mice, Felix Rivera-Molina and Derek K. Toomre for assistance with spinning disk microscopy, and Elias Lolis for the MIP2 proteins ( Rajasekaran et al., 2012 ). The work is supported by National Institutes of Health grants to D.W. ( R35HL135805 ), W.T. ( R01HL145152 ), E.K. ( R01GM108954 and R01GM114513 ), Z.S. ( R01HL125885 ), and F.P. ( R01NSNS067557 ) and the Snyder Mouse Phenomics Resources Laboratory and Live Cell Imaging Facility, both of which were funded by the Snyder Institute for Chronic Diseases at the University of Calgary , Calgary, Canada. We thank Michelle Orsulak for technical assistance, Pietro De Camilli for providing PIP5K1C antibody (Di Paolo et al. 2002) and human PI4KA cDNA, Guangxin Li and George Tellides for the mT/mG mice, Felix Rivera-Molina and Derek K. Toomre for assistance with spinning disk microscopy, and Elias Lolis for the MIP2 proteins (Rajasekaran et al. 2012). The work is supported by National Institutes of Health grants to D.W. (R35HL135805), W.T. (R01HL145152), E.K. (R01GM108954 and R01GM114513), Z.S. (R01HL125885), and F.P. (R01NSNS067557) and the Snyder Mouse Phenomics Resources Laboratory and Live Cell Imaging Facility, both of which were funded by the Snyder Institute for Chronic Diseases at the University of Calgary, Calgary, Canada. D.W. W.T. and E.K. supervised the project and developed the concepts. C.R. Q.Y. M.B. X.Z. B.P. J.Z. D.K. J.G.-H. and W.X. performed the experiments and analyzed the data. D.W. W.T. E.K. C.R. Q.Y. M.B. D.K. R.F. B.P. P.K. W.P. Z.S. Y.O. and F.P. designed the experiments and wrote the paper. All authors were involved in the writing and final approval of the manuscript. The authors declare no competing interests.

FundersFunder number
Live Cell Imaging Facility
Snyder Mouse Phenomics Resources Laboratory
National Institutes of HealthR01HL145152, R35HL135805, R01GM114513, R01NSNS067557, R01HL125885
National Institute of General Medical SciencesR01GM108954
University of Calgary

    Keywords

    • BAR domain
    • SRGAP2
    • adhesion
    • cell polarization
    • neutrophil
    • phosphatidylinositol-4-phosphate

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