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Journal Article

Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness

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Erdmann,  Philipp S.
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Hou,  Zhen
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Plitzko,  Jürgen
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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s41467-020-14544-1.pdf
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Citation

Wong, L. E., Bhatt, A., Erdmann, P. S., Hou, Z., Maier, J., Pirkuliyeva, S., et al. (2020). Tripartite phase separation of two signal effectors with vesicles priming B cell responsiveness. Nature Communications, 11(1): 848. doi:10.1038/s41467-020-14544-1.


Cite as: https://hdl.handle.net/21.11116/0000-0005-FA55-2
Abstract
Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and the proper engagement of its intracellular signal effector proteins. Src homology (SH) 2 domain-containing leukocyte protein of 65 kDa (SLP65) is the key scaffold protein mediating BCR signaling. In resting B cells, SLP65 colocalizes with Cbl-interacting protein of 85 kDa (CIN85) in cytoplasmic granules whose formation is not fully understood. Here we show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles into droplets via vesicle binding of SLP65 and promiscuous interactions between nine SH3 domains of the trimeric CIN85 and the proline-rich motifs (PRMs) of SLP65. Vesicles are clustered and the dynamical structure of SLP65 persists in the droplet phase in vitro. Our results demonstrate that phase separation driven by concerted transient interactions between scaffold proteins and vesicles is a cellular mechanism to concentrate and organize signal transducers.
Antibody-mediated immune responses rely on antigen recognition by the B cell antigen receptor (BCR) and SLP65 is a key scaffold protein mediating BCR signaling. Here authors show that effective B cell activation requires tripartite phase separation of SLP65, CIN85, and lipid vesicles.