Article

The Membrane Skeleton Controls Diffusion Dynamics and Signaling through the B Cell Receptor

Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Immunity (Impact Factor: 21.56). 02/2010; 32(2):187-99. DOI: 10.1016/j.immuni.2009.12.005
Source: PubMed

ABSTRACT

Early events of B cell activation after B cell receptor (BCR) triggering have been well characterized. However, little is known about the steady state of the BCR on the cell surface. Here, we simultaneously visualize single BCR particles and components of the membrane skeleton. We show that an ezrin- and actin-defined network influenced steady-state BCR diffusion by creating boundaries that restrict BCR diffusion. We identified the intracellular domain of Igbeta as important in mediating this restriction in diffusion. Importantly, alteration of this network was sufficient to induce robust intracellular signaling and concomitant increase in BCR mobility. Moreover, by using B cells deficient in key signaling molecules, we show that this signaling was most probably initiated by the BCR. Thus, our results suggest the membrane skeleton plays a crucial function in controlling BCR dynamics and thereby signaling, in a way that could be important for understanding tonic signaling necessary for B cell development and survival.

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Available from: Facundo Batista, Apr 12, 2014
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    • "The cytoskeleton and associated proteins define membrane compartments, restricting the diffusion of plasma membrane components (Kusumi et al, 1993Kusumi et al, , 2005) such as FceRI in mast cells and the BCR on B-cell membranes (Andrews et al, 2008; Treanor et al, 2010). In particular, the lateral mobility of the BCR is mediated by the cortical cytoskeleton (Treanor et al, 2010). This interaction has profound consequences for signalling, evidenced by BCR signalling after cytoskeleton disruption. "
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    • "In addition, TLR signaling has been shown to influence actin organization , thereby increasing BCR mobility and facilitating BCR signaling (Freeman et al., 2015). Furthermore, changes in actin organization alone increases BCR diffusion and triggers signaling similar to BCR crosslinking (Treanor et al., 2010). This ligand-independent signal not only requires increased BCR diffusion but also an immobilized co-receptor CD19, held in place by its association with the tetraspanin molecule CD81 (Mattila et al., 2013). "
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    • "The cytoskeleton was previously shown to restrict diffusion of membrane proteins, such as the BCR, Fcγ receptor, and CD36, thereby modulating their signaling. To our knowledge, this is the first demonstration that the actin cytoskeleton regulates physical contact between a membrane protease and its substrate (Treanor et al., 2010; Jaqaman et al., 2011; Jaumouille et al., 2014). Several factors could regulate such an exclusion mechanism. "
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