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

Ivan Rey-Suarez, Brittany A. Wheatley, Peter Koo, Anshuman Bhanja, Zhou Shu, Simon Mochrie, Wenxia Song, Hari Shroff and Arpita Upadhyaya ()
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Ivan Rey-Suarez: University of Maryland
Brittany A. Wheatley: University of Maryland
Peter Koo: Harvard University
Anshuman Bhanja: University of Maryland
Zhou Shu: University of Maryland
Simon Mochrie: Yale University
Wenxia Song: University of Maryland
Hari Shroff: National Institutes of Health
Arpita Upadhyaya: University of Maryland

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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 FcγRIIB, 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14335-8

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DOI: 10.1038/s41467-020-14335-8

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