Rap1 orchestrates cytoskeletal remodelling at the immune synapse

Antigen-presenting cells (APCs) display antigens on their surface, which are recognised by the B cell receptor (BCR). Signal transduction and antigen internalisation by the BCR are facilitated by BCR-induced reorganisation of the actin and microtubule (MT) cytoskeleton. This in turn promotes the coalescence of BCR microclusters into a central supramolecular activation cluster (cSMAC) to form the immune synapse. Because the pathways for the coordination of actin and MT networks at the immune synapse are not fully understood, Jia Wang, Michael Gold and colleagues now (p. 1094) investigate the role of the Rap1 GTPase in the polarisation of the microtubule-organising centre (MTOC) towards the immune synapse. The authors show that both MT and Rap1 are required for cSMAC formation. Importantly, Rap1, as well as the actin-severing activity of the Rap1 target cofilin-1, are needed for BCR-induced polarisation of the MTOC towards the immune synapse. Furthermore, MTOC polarisation also depends on the motor protein dynein, the actin–MT crosslinker IQGAP1 and the protein CLIP-170, which binds to MT plus-ends. As shown here, both IQGAP1 and CLIP-170 localise to MT–actin interfaces, with Rap1 reorganising the actin cytoskeleton to promote IQGAP1 accumulation at the periphery of the immune synapse. Taken together, this work establishes a role for the Rap1–cofilin-1 pathway in coordinating cytoskeletal reorganisation at the B cell immune synapse and promoting MTOC polarisation towards the APC.