Sci. STKE, 27 April 2004
IMMUNOLOGY Deacetylating Microtubules at the Immune Synapse
T cell activation by antigen-presenting cells (APCs) involves formation of the immune synapse, a specialized junction characterized by supramolecular clusters of antigen receptors and other signaling molecules. Although the actin cytoskeleton has been implicated in this process, the role of microtubules in T cell activation is less well understood. Serrador et al. used immunocytochemistry combined with confocal microscopy to show that acetylated microtubules were concentrated in areas of conjugation between Jurkat T cells and APCs, where they surrounded clusters of CD3 and the integrin LFA-1. T cell-APC engagement was accompanied by an initial brief decrease in tubulin acetylation, followed by an increase. HDAC6 (which deacetylates α-tubulin) concentrated at sites of T cell-APC contact and redistributed from the central contact region to the periphery as the immunological synapse matured. Overexpression of green fluorescent protein (GFP)-labeled HDAC6 led to decreased acetylation of microtubules at contact regions and inhibited clustering of CD3 in the central region of the immune synapse and of LFA-1 in the periphery, whereas expression of an acetylase-dead mutant did not. The HDAC6 inhibitor trichostatin, whose application was associated with intense staining for acetylated α-tubulin at contact regions, blocked the effects of HDAC6 overexpression and accelerated CD3 clustering. Similarly, siRNA knockdown of HDAC6, which decreased tubulin acetylation, promoted CD3 clustering. HDAC6 overexpression also inhibited reorientation of the microtubule-organizing center, another process associated with T cell activation, and blocked production of interleukin-2. These data implicate HDAC6 activity in T cell activation and development of the immune synapse and suggest that its effects may be mediated through localized deacetylation of microtubules.
J. M. Serrador, J. R. Cabrero, D. Sancho, M. Mittelbrunn, A. Urzainqui, F. Sánchez-Madrid, HDAC6 deacetylase activity links the tubulin cytoskeleton with immune synapse organization. Immunity 20, 417-428 (2004). [Online Journal]
Citation: Deacetylating Microtubules at the Immune Synapse. Sci. STKE 2004, tw148 (2004).
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