Tetraspanin microdomains control localized protein kinase C signaling in B cells.

Autor:	Zuidscherwoude M; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., Dunlock VE; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., van den Bogaart G; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., van Deventer SJ; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., van der Schaaf A; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., van Oostrum J; Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., Goedhart J; Swammerdam Institute for Life Sciences, Section of Molecular Cytology, van Leeuwenhoek Centre for Advanced Microscopy, University of Amsterdam, 1098 XH Amsterdam, Netherlands., In 't Hout J; Department for Health Evidence, Radboud Institute for Health Sciences, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands., Hämmerling GJ; Department of Molecular Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Tanaka S; Department of Pathology, Sapporo Medical University School of Medicine, 060-8556 Sapporo, Japan., Nadler A; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany., Schultz C; Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany., Wright MD; Department of Immunology, Monash University, Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia., Adjobo-Hermans MJW; Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands., van Spriel AB; Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands. annemiek.vanspriel@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	Science signaling [Sci Signal] 2017 May 09; Vol. 10 (478). Date of Electronic Publication: 2017 May 09.
DOI:	10.1126/scisignal.aag2755
Abstrakt:	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. (Copyright © 2017, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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