Research ArticleImmunology

The adaptor protein CIN85 assembles intracellular signaling clusters for B cell activation

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Science Signaling  28 Jun 2016:
Vol. 9, Issue 434, pp. ra66
DOI: 10.1126/scisignal.aad6275

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Controlling signaling through clustering

Several cell surface receptors require the multidomain protein CIN85 for signaling. Kühn et al. elucidated its mode of action in B lymphocytes in which CIN85 associates with the adaptor protein SLP-65, which transmits activation signals from the B cell receptor (BCR). NMR spectroscopy and X-ray crystallography showed that CIN85 formed a stable trimer through its C-terminal, coiled-coil domain. The SH3 domains of CIN85 recruited multiple SLP-65 molecules that in turn bound to other CIN85 trimers, resulting in the formation of large CIN85–SLP-65 signaling clusters. Manipulating the oligomerization state of SLP-65 affected the efficiency of BCR signaling, which suggests that CIN85 sets the threshold for B cell activation by controlling the size of SLP-65 signaling clusters.

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