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Publication : B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster.

First Author  Schnyder T Year  2011
Journal  Immunity Volume  34
Issue  6 Pages  905-18
PubMed ID  21703542 Mgi Jnum  J:173993
Mgi Id  MGI:5050759 Doi  10.1016/j.immuni.2011.06.001
Citation  Schnyder T, et al. (2011) B cell receptor-mediated antigen gathering requires ubiquitin ligase cbl and adaptors grb2 and dok-3 to recruit Dynein to the signaling microcluster. Immunity 34(6):905-18
abstractText  The B cell receptor (BCR) mediates B cell antigen gathering and acquisition for presentation to T cells. Although the amount of antigen presentation to T cells determines the extent of B cell activation, the molecular mechanisms underlying antigen gathering remain unexplored. Here, through a combination of high-resolution imaging, genetics and quantitative mass spectrometry, we demonstrate that adaptors Grb2 and Dok-3, and ubiquitin ligase Cbl in signaling BCR microclusters mediate association with the microtubule motor dynein. Furthermore, we visualize the localization and movement of these microclusters on the underlying microtubule network. Importantly, disruption of this network or diminished dynein recruitment in Grb2-, Dok-3-, or Cbl-deficient B cells, does not influence microcluster formation or actin-dependent spreading, but abrogates directed movement of microclusters and antigen accumulation. Thus we identify a surprising but pivotal role for dynein and the microtubule network alongside Grb2, Dok-3, and Cbl in antigen gathering during B cell activation.
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