Membrane–cytoskeleton interactions during the formation of the immunological synapse and subsequent T‐cell activation

Abstract

Upon antigen recognition, T cells undergo substantial membrane and cytoskeletal rearrangements that lead to the formation of the immunological synapse and are necessary for subsequent T-cell activation. However, little is known about how membrane and cytoskeletal molecules interact during these processes. Here we discuss the involvement of the membrane-microfilament linker ezrin. We propose that ezrin is a component of the cytoskeleton-mediated architecture of the immunological synapse that plays a role in T-cell receptor clustering, protein kinase C theta translocation and intracellular signaling.

The Ca2+-activated K+ channel KCa3.1 compartmentalizes in the immunological synapse of human T lymphocytes

“…Interestingly it appears that F-actin is concentrated mostly on the periphery of the T cell-bead contact point after 30 min of activation as previously shown, whereas KCa3.1 channels acquire a more central localization (Fig. 3, "xz projection") (2,5). These studies indicate that KCa3.1 channels reorganize at the T cell-bead interface on conjugation.…”

“…This is characterized by an extensive reorganization of the actin cytoskeleton and specific membrane (TCR and adhesion molecules) and signaling proteins to the T cell-APC contact interface (5,9,20). In the present study, we demonstrate that KCa3.1 channels are evenly distributed on the membrane of human T lymphocytes but translocate to the IS on encounter with an APC and become part of the signaling complex that facilitates T cell proliferation and cytokine production.…”

“…This is a wellvalidated system shown by us and others to induce Ca 2ϩ influx and molecular reorganization, both indicative of a functional T cell activation (23,30). Furthermore, upon T cell activation, extensive cytoskeletal reorganization takes place, resulting in F-actin accumulation at the contact point; as such, it can serve as a marker of IS formation (3,5). The YFP-KCa3.1 channels were expressed in preactivated human T cells and were prepared for immunocytochemistry experiments 6 h after transfection.…”

Involvement of filamentous actin in setting the threshold for degranulation in mast cells

“…Tyrosine phosphorylation of ezrin, a compound which functions as a linker between the actin skeleton and integral plasma membrane proteins [17], was strongly inhibited by pretreatment with latrunculin in both Thy-1-and Fc 4 RI-activated cells. This inhibition was not attributable to a decreased amount of ezrin immunoprecipitated from saponin/Triton X-100-solubilized cells, as inferred from the results of immunoblotting with anti-ezrin Ab (Fig.…”

Subcellular dynamics of T cell immunological synapses and kinapses in lymph nodes

“…1). Reorganization of the actin cytoskeleton (2,3), translocation of the microtubule organizing center (4,5), segregation of surface and signaling molecules into central and peripheral regions of the contact zone (cSMAC and pSMAC, respectively) (6, 7), condensation of membrane microdomains (8), and formation of dynamic microclusters (9)(10)(11)(12)(13) contribute to immunological synapse formation and have been proposed to participate in and/or regulate T cell activation. Of note, the topology of the immunological synapse is not unique and may depend on the type of APC, the T cell phenotype, and the strength of stimulation (14)(15)(16).…”