Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement.
Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement.
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DOI：
10.1016/j.cell.2017.12.023
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发表时间：
2018-01-11
期刊：
影响因子：
64.5
通讯作者：
Grinstein S
中科院分区：
文献类型：
--
作者：
Freeman SA;Vega A;Riedl M;Collins RF;Ostrowski PP;Woods EC;Bertozzi CR;Tammi MI;Lidke DS;Johnson P;Mayor S;Jaqaman K;Grinstein S
吞噬受体必须横向扩散，以在被多价靶标聚集时被激活。然而，受体扩散可以被通过与皮质细胞骨架相互作用而固定的跨膜蛋白（“尖桩”）阻碍。这些尖突的分子特性及其在吞噬作用中的作用尚未确定。我们使用单分子追踪来研究Fcγ受体与CD 44之间的相互作用，CD 44是一种丰富的跨膜蛋白，能够与F-actin间接缔合，因此可能充当纠察。CD 44可逆地束缚于形成素诱导的肌动蛋白丝，减少受体扩散。这种线性细丝在极化的巨噬细胞的尾端占主导地位，在那里受体的迁移率是最小的。相反，受体是最移动的在前沿，Arp 2/3驱动的肌动蛋白分支占主导地位。CD 44与透明质酸结合，锚定细胞外被，这也限制了受体置换并阻碍了吞噬靶点的进入。必须施加力才能穿过细胞周围屏障，使受体能够与其靶标结合。
Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins (“pickets”) that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket. CD44 tethers reversibly to formin-induced actin filaments, curtailing receptor diffusion. Such linear filaments predominate in the trailing end of polarized macrophages, where receptor mobility was minimal. Conversely, receptors were most mobile at the leading edge, where Arp2/3-driven actin branching predominates. CD44 binds hyaluronan, anchoring a pericellular coat that also limits receptor displacement and obstructs access to phagocytic targets. Force must be applied to traverse the pericellular barrier, enabling receptors to engage their targets.
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影响因子：
4
作者：
Schwartz, Samantha L.;Yan, Oi;Telmer, Cheryl A.;Lidke, Keith A.;Bruchez, Marcel P.;Lidke, Diane S.
通讯作者：
Lidke, Diane S.
影响因子：
2.2
作者：
Segura, I;Casadesús, J;Ramos-Morales, F
通讯作者：
Ramos-Morales, F
影响因子：
30.5
作者：
Faure, S;Salazar-Fontana, LI;Delon, J
通讯作者：
Delon, J
影响因子：
7.8
作者：
Fujiwara, Takahiro;Ritchie, Ken;Murakoshi, Hideji;Jacobson, Ken;Kusumi, Akihiro
通讯作者：
Kusumi, Akihiro
影响因子：
64.8
作者：
Laemmermann, Tim;Bader, Bernhard L.;Sixt, Michael
通讯作者：
Sixt, Michael