Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment.
Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment.
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DOI：
10.1016/j.devcel.2019.02.023
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发表时间：
2019-04
影响因子：
11.8
通讯作者：
Chunguang Ren;Qianying Yuan;M. Braun;Xia Zhang;B. Petri;Jiasheng Zhang;Dongjoo Kim;J. Guez-Haddad;Wenzhi Xue;Weijun Pan;R. Fan;P. Kubes;Zhaoxia Sun;Y. Opatowsky;F. Polleux;E. Karatekin;Wenwen Tang;Dianqing Wu
中科院分区：
文献类型：
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作者：
Chunguang Ren;Qianying Yuan;M. Braun;Xia Zhang;B. Petri;Jiasheng Zhang;Dongjoo Kim;J. Guez-Haddad;Wenzhi Xue;Weijun Pan;R. Fan;P. Kubes;Zhaoxia Sun;Y. Opatowsky;F. Polleux;E. Karatekin;Wenwen Tang;Dianqing Wu
细胞极化对于各种生物过程都很重要。然而，其调节，特别是启动，尚不完全清楚。在这里，我们研究了中性粒细胞打破其对称性并启动其细胞骨架从循环中的非极性状态极化以在炎症期间外渗的机制。我们在这里表明，细胞与表面接触导致质膜（PM）曲率的局部增加触发了非极性中性粒细胞对称性的初始破坏，并且是化学刺激引起的后续极化事件所必需的。 PM 曲率的这种局部增加通过其 F-BAR 结构域招募 SRGAP2，进而激活 PI4KA 并导致 PM PtdIns4P 极化。极化的 PM PtdIns4P 是 RPH3A 的靶标，RPH3A 指导 PIP5K1C90 和随后的磷酸化肌球蛋白轻链极化，并且该极化信号轴调节中性粒细胞与内皮的牢固附着。因此，这项研究揭示了细胞骨架极化的启动机制。
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.