Tetraspanin microdomains control localized protein kinase C signaling in B cellsZuidscherwoude, M., Dunlock, V-M. E., van den Bogaart, G., van Deventer, S. J., van der Schaaf, A., van Oostrum, J., Goedhart, J., 't Hout, J. I., Haemmerling, G. J., Tanaka, S., Nadler, A., Schultz, C., Wright, M. D., Adjobo-Hermans, M. J. W. & van Spriel, A. B., 9-May-2017, In : Science signaling. 10, 478, 15 p., 2755.
Research output: Contribution to journal › Article › Academic › peer-review
Activation of B cells by the binding of antigens to the B cell receptor (BCR) requires the protein kinase C (PKC) family member PKC beta. Because PKCs must translocate to the plasma membrane to become activated, we investigated the mechanisms regulating their spatial distribution in mouse and human B cells. Through live-cell imaging, we showed that BCR-stimulated production of the second messenger diacylglycerol (DAG) resulted in the translocation of PKC beta from the cytosol to plasma membrane regions containing the tetraspanin protein CD53. CD53 was specifically enriched at sites of BCR signaling, suggesting that BCR-dependent PKC signaling was initiated at these tetraspanin microdomains. Fluorescence lifetime imaging microscopy studies confirmed the molecular recruitment of PKC to CD53-containing microdomains, which required the amino terminus of CD53. Furthermore, we showed that Cd53-deficient B cells were defective in the phosphorylation of PKC substrates. Consistent with this finding, PKC recruitment to the plasma membrane was impaired in both mouse and human CD53-deficient B cells compared to that in their wild-type counterparts. These data suggest that CD53 promotes BCR-dependent PKC signaling by recruiting PKC to the plasma membrane so that it can phosphorylate its substrates and that tetraspanin-containing microdomains can act as signaling hotspots in the plasma membrane.
|Number of pages||15|
|Publication status||Published - 9-May-2017|
- FLUORESCENT PROTEINS, MAMMALIAN-CELLS, PKC-BETA, ACTIVATION, INTEGRINS, CD53, COMPLEXES, DOMAINS, CD37, CD81