Research ArticleImmunology

Tetraspanin microdomains control localized protein kinase C signaling in B cells

See allHide authors and affiliations

Science Signaling  09 May 2017:
Vol. 10, Issue 478, eaag2755
DOI: 10.1126/scisignal.aag2755

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Kinase recruiting by a tetraspanin

The protein kinase C (PKC) family member PKCβ mediates antigen-dependent B cell receptor (BCR) signaling to activate B cells. Mice deficient in the PKCβ isoform have defective antibody responses, whereas PKCβ-specific inhibitors are under investigation for the treatment of B cell malignancies. Using live-cell imaging of mouse and human B cells, Zuidscherwoude et al. showed that, in response to BCR stimulation, PKCβ was specifically and transiently recruited to plasma membrane microdomains enriched in the tetraspanin protein CD53. Mouse or human B cells deficient in CD53, but not other tetraspanins, showed impaired PKCβ activation and reduced phosphorylation of its targets, suggesting that CD53-containing membrane regions act as platforms for the activation of PKCβ in these cells.


Activation of B cells by the binding of antigens to the B cell receptor (BCR) requires the protein kinase C (PKC) family member PKCβ. 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 PKCβ 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.

View Full Text

Stay Connected to Science Signaling