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Sci Signal. 2014 Aug 19;7(339):ra79. doi: 10.1126/scitranslmed.2005104.

Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells.

Author information

1
Institute of Cellular and Molecular Immunology, Georg August University of Göttingen, Humboldtallee 34, 37073 Göttingen, Germany.
2
Department of NMR-Based Structural Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
3
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
4
Institute of Cellular and Molecular Immunology, Georg August University of Göttingen, Humboldtallee 34, 37073 Göttingen, Germany. jwienan@gwdg.de.

Abstract

The traditional view of how intracellular effector proteins are recruited to the B cell antigen receptor (BCR) complex at the plasma membrane is based on the occurrence of direct protein-protein interactions, as exemplified by the recruitment of the tyrosine kinase Syk (spleen tyrosine kinase) to phosphorylated motifs in BCR signaling subunits. By contrast, the subcellular targeting of the cytosolic adaptor protein SLP-65 (Src homology 2 domain-containing leukocyte adaptor protein of 65 kD), which serves as a proximal Syk substrate, is unclear. We showed that SLP-65 activation required its association at vesicular compartments in resting B cells. A module of ~50 amino acid residues located at the amino terminus of SLP-65 anchored SLP-65 to the vesicles. Nuclear magnetic resonance spectroscopy showed that the SLP-65 amino terminus was structurally disordered in solution but could bind in a structured manner to noncharged lipid components of cellular membranes. Our finding that preformed vesicular signaling scaffolds are required for B cell activation indicates that vesicles may deliver preassembled signaling cargo to sites of BCR activation.

PMID:
25140054
DOI:
10.1126/scitranslmed.2005104
[Indexed for MEDLINE]

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