Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor

Citations Over TimeTop 10% of 2015 papers

Abstract

Integrating signals from multiple receptors allows cells to interpret the physiological context in which a signal is received. Here we describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signalling by another receptor. We show that the Toll-like receptor ligands lipopolysaccharide and CpG DNA, which are conserved microbial molecules, enhance signalling by the B-cell antigen receptor (BCR) by activating the actin-severing protein cofilin. Single-particle tracking reveals that increased severing of actin filaments reduces the spatial confinement of the BCR within the plasma membrane and increases BCR mobility. This allows more frequent collisions between BCRs and greater signalling in response to low densities of membrane-bound antigen. These findings implicate actin dynamics as a means of tuning receptor signalling and as a mechanism by which B cells distinguish inert antigens from those that are accompanied by indicators of microbial infection.

Related Papers

• → Networks and crosstalk: integrin signalling spreads(2002)798 cited
• → The integration of reactive oxygen species (ROS) and calcium signalling in abiotic stress responses(2023)200 cited
• → Improving Orthogonality in Two-Component Biological Signalling Systems Using Feedback Control(2018)6 cited
• → Reactive Oxygen Species as Signalling Molecules(2005)53 cited
• → ROS Crosstalk in Signalling Pathways(2020)2 cited