Gradients of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling

被引：66

作者：

Remorino, Amanda ^{[1
]}

De Beco, Simon ^{[1
]}

Cayrac, Fanny ^{[1
]}

Di Federico, Fahima ^{[1
]}

Cornilleau, Gaetan ^{[1
]}

Gautreau, Alexis ^{[2
]}

Parrini, Maria Carla ^{[3
]}

Masson, Jean-Baptiste ^{[4
,5
]}

Dahan, Maxime ^{[1
]}

Coppey, Mathieu ^{[1
]}

机构：

[1] Univ Pierre & Marie Curie Paris 6, Lab Physico Chim, Inst Curie, CNRS,UMR168,Paris Sci Lettres, F-75005 Paris, France

[2] Univ Paris Saclay, Ecole Polytech, CNRS, UMR7654, F-91120 Palaiseau, France

[3] Inst Curie, Ctr Rech, Paris Sci Lettres, ART Grp,Inserm,U830, F-75005 Paris, France

[4] Inst Pasteur, Decis & Bayesian Computat, 25 Rue Docteur Roux, F-75015 Paris, France

[5] CNRS, IP, USR 3756, Bioinformat & Biostat Hub C3BI, Paris, France

来源：

CELL REPORTS | 2017年 / 21卷 / 07期

关键词：

PLASMA-MEMBRANE; ACTIN DYNAMICS; H-RAS; PROTEIN; BINDING; ACTIVATION; CLUSTERS; SEGREGATION; INTEGRINS; MIGRATION;

D O I：

10.1016/j.celrep.2017.10.069

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Rac1 is a small RhoGTPase switch that orchestrates actin branching in space and time and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single-molecule imaging and super-resolution microscopy, we show an additional supramolecular organization of Rac1. We find that Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each. These nanoclusters assemble because of the interaction of the polybasic tail of Rac1 with the phosphoinositide lipids PIP2 and PIP3. The additional interactions with GEFs and possibly GAPs, downstream effectors, and other partners are responsible for an enrichment of Rac1 nanoclusters in protruding regions of the cell. Our results show that subcellular patterns of Rac1 activity are supported by gradients of signaling nanodomains of heterogeneous molecular composition, which presumably act as discrete signaling platforms.

引用

页码：1922 / 1935

页数：14

共 77 条

[21] Using plasma membrane nanoclusters to build better signaling circuits [J].