Unknown

Dataset Information

0

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


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 Fc?RIIB, 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.

SUBMITTER: Rey-Suarez I 

PROVIDER: S-EPMC6978525 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Rey-Suarez Ivan I   Wheatley Brittany A BA   Koo Peter P   Bhanja Anshuman A   Shu Zhou Z   Mochrie Simon S   Song Wenxia W   Shroff Hari H   Upadhyaya Arpita A  

Nature communications 20200123 1


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 act  ...[more]

Similar Datasets

| S-EPMC3907214 | biostudies-other
| S-EPMC133613 | biostudies-literature
| S-EPMC2718491 | biostudies-literature
| S-EPMC6446838 | biostudies-literature
| S-EPMC10613254 | biostudies-literature
| S-EPMC7013255 | biostudies-literature
| S-EPMC4263859 | biostudies-literature
| S-EPMC4159282 | biostudies-literature
| S-EPMC2290849 | biostudies-literature
| S-EPMC2921111 | biostudies-literature