RT Journal Article
T1 Separating Actin-Dependent Chemokine Receptor Nanoclustering from Dimerization Indicates a Role for Clustering in CXCR4 Signaling and Function.
A1 Martínez-Muñoz, Laura
A1 Rodríguez-Frade, José Miguel
A1 Barroso, Rubén
A1 Sorzano, Carlos Óscar S
A1 Torreño-Pina, Juan A
A1 Santiago, César A
A1 Manzo, Carlo
A1 Lucas, Pilar
A1 García-Cuesta, Eva M
A1 Gutierrez, Enric
A1 Barrio, Laura
A1 Vargas, Javier
A1 Cascio, Graciela
A1 Carrasco, Yolanda R
A1 Sánchez-Madrid, Francisco
A1 García-Parajo, María F
A1 Mellado, Mario
K1 GPCR
K1 TIRF
K1 chemokine receptors
K1 chemokines
K1 live cell imaging
K1 receptor clustering
K1 receptor dynamics
K1 single particle tracking
AB A current challenge in cell motility studies is to understand the molecular and physical mechanisms that govern chemokine receptor nanoscale organization at the cell membrane, and their influence on cell response. Using single-particle tracking and super-resolution microscopy, we found that the chemokine receptor CXCR4 forms basal nanoclusters in resting T cells, whose extent, dynamics, and signaling strength are modulated by the orchestrated action of the actin cytoskeleton, the co-receptor CD4, and its ligand CXCL12. We identified three CXCR4 structural residues that are crucial for nanoclustering and generated an oligomerization-defective mutant that dimerized but did not form nanoclusters in response to CXCL12, which severely impaired signaling. Overall, our data provide new insights to the field of chemokine biology by showing that receptor dimerization in the absence of nanoclustering is unable to fully support CXCL12-mediated responses, including signaling and cell function in vivo.
YR 2018
FD 2018
LK http://hdl.handle.net/10668/12317
UL http://hdl.handle.net/10668/12317
LA en
DS RISalud
RD Apr 7, 2025