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Publication : WASP family proteins regulate the mobility of the B cell receptor during signaling activation.

First Author  Rey-Suarez I Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  439
PubMed ID  31974357 Mgi Jnum  J:285642
Mgi Id  MGI:6387656 Doi  10.1038/s41467-020-14335-8
Citation  Rey-Suarez I, et al. (2020) WASP family proteins regulate the mobility of the B cell receptor during signaling activation. Nat Commun 11(1):439
abstractText  Regulation of membrane receptor mobility tunes cellular response to external signals, such as in binding of B cell receptors (BCR) to antigen, which initiates signaling. However, whether BCR signaling is regulated by BCR mobility, and what factors mediate this regulation, are not well understood. Here we use single molecule imaging to examine BCR movement during signaling activation and a novel machine learning method to classify BCR trajectories into distinct diffusive states. Inhibition of actin dynamics downstream of the actin nucleating factors, Arp2/3 and formin, decreases BCR mobility. Constitutive loss or acute inhibition of the Arp2/3 regulator, N-WASP, which is associated with enhanced signaling, increases the proportion of BCR trajectories with lower diffusivity. Furthermore, loss of N-WASP reduces the diffusivity of CD19, a stimulatory co-receptor, but not that of FcgammaRIIB, an inhibitory co-receptor. Our results implicate a dynamic actin network in fine-tuning receptor mobility and receptor-ligand interactions for modulating B cell signaling.
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