Cell adhesion molecules and actin cytoskeleton at immune synapses and kinapses

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The immunological synapse is a stable adhesive junction between a polarized immune effector cell and an antigen-bearing cell. Immunological synapses are often observed to have a striking radial symmetry in the plane of contact with a prominent central cluster of antigen receptors surrounded by concentric rings of adhesion molecules and actin-rich projections. There is a striking similarity between the radial zones of the immunological synapse and the dynamic actinomyosin modules employed by migrating cells. Breaking the symmetry of an immunological synapse generates a moving adhesive junction that can be defined as a kinapse, which facilitates signal integration by immune cells while moving over the surface of antigen-presenting cells.

Section snippets

Signaling and adhesion structures in T cell activation

TCR signaling is based on a tyrosine kinase cascade that leads to rapid activation of phospholipase C γ [4]. The triggering of the cascade is based on recruitment and activation of Lck. A model incorporating feedback loops involving the activation of the serine/threonine kinase Erk and adapters including Unc 119 or TsAD, which increase activation of Lck in an agonist MHCp-dependent fashion, and SHP-1, which is recruited in place of ZAP-70 to partially phosphorylated TCR and negatively regulates

Continuous formation of TCR microclusters in periphery sustains signaling

TCR signaling is initiated before cSMAC formation [25, 26]. The formation of the cSMAC takes place through convergence of TCR clusters that form during initial contact formation and are actively transported to the center [26]. Application of total internal reflection fluorescence microscopy (TIRFM) to the IS led to a striking discovery that this centripetal transport of TCR clusters is continuous during T cell activation [26, 27•, 28]. Microclusters form at the outer edge of the IS and move at 1

Relationship of SMACs to cell motility modules

Fibroblast spreading on fibronectin-coated glass has revealed the modular nature of cell migration [29••]. The rapid phase of contact expansion is driven by actin polymerization at the outer edge while forming a radially symmetric sheet of f-actin close to the contact surface. Once the contact area reaches its maximal size, the f-actin layer continues to undergo polymerization at the edge, and this results in centripital actin flow. At this stage a new f-actin layer forms on top of the first

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

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Acknowledgements

I thank R Varma, G Campi, T Sims, T Cameron, P Velazquez, J Kim, G Shakhar, M Nussenzweig, and ME Dustin for valuable discussions. This work was supported by the NIH and the Irene Diamond Fund.

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