期刊
EMBO JOURNAL
卷 35, 期 3, 页码 258-280出版社
WILEY
DOI: 10.15252/embj.201593027
关键词
B-cell receptor signalling; glycoprotein CD45; membrane dynamics; siglec CD22; super-resolution microscopy
资金
- Cancer Research UK, Institute Pasteur-Fondazione Cenci Bolognetti
- Royal Society Wolfson Research Merit Award
Receptor organization and dynamics at the cell membrane are important factors of signal transduction regulation. Using super-resolution microscopy and single-particle tracking, we show how the negative coreceptor CD22 works with the cortical cytoskeleton in restraining BCR signalling. In naive B cells, we found endogenous CD22 to be highly mobile and organized into nanodomains. The landscape of CD22 and its lateral diffusion were perturbed either in the absence of CD45 or when the CD22 lectin domain was mutated. To understand how a relatively low number of CD22 molecules can keep BCR signalling in check, we generated Brownian dynamic simulations and supported them with exvivo experiments. This combined approach suggests that the inhibitory function of CD22 is influenced by its nanoscale organization and is ensured by its fast diffusion enabling a global BCR surveillance at the plasma membrane.
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