Localizing order to boost signaling

Abstract

B-cell receptors form ordered clusters to recruit kinases and exclude phosphatases.

Keywords: biophysics; immunology; lipid raft; membrane phase separation; mouse; structural biology; super-resolution microscopy.

Figure 1.. B cell receptors and liquid-ordered domains.

(A) In the model proposed by Stone et al., B cell receptors (BCRs) cluster and intrinsically interact with liquid-ordered domains. The interaction of the receptors with antigens (Ag) stabilizes an extended liquid-ordered domain (around 100 nanometers in diameter) through protein-lipid interactions that recruit kinases (such as Lyn) and exclude phosphatases (such as CD45). (B) In an alternative protein-protein interaction model, B cell receptors do not interact with liquid-ordered domains, but antigen binding causes the receptors to cluster. This initiates interactions between the receptors and lipid-modified kinases, which then recruit liquid-ordered domains that provide further feed forward effects, such as CD45 exclusion, to allow efficient phosphorylation. (C) In the dissociation activation model, the receptors cluster to produce a structure in which kinases cannot access the sites they would normally phosphorylate. The binding of antigens to the receptors disrupts the clusters, leading to the recruitment of kinases and the formation of looser clusters that resemble liquid-ordered domains.