DISC1 is needed for the organization of cellular components at the immunological synapse.

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2019-04

Authors

Ramakrishnan, Adarsh

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Abstract

T-cells carry out their immune functions through receptor-based recognition and adhesion to target cells. The cell-cell junction that is created from this connection is known as the immunological synapse (IS); a cellular structure composed of organized receptor clusters. Polymerization of F-actin at the synapse has been cited as a necessary step in the continuous activation and flow of T-cell receptors (TCR) towards the center of the synapse and activation of the integrin, Lymphocyte Function Associated Antigen 1 (LFA-1). These processes help T-cells form stable and specific connections with their cognate Antigen Presenting Cells (APCs). It has been previously shown that Disrupted in Schizophrenia 1 (DISC1), a protein with connections to actin-based signaling in neurons, is expressed in T-cells. Through immunofluorescence techniques and CRISPR-Cas9 knockout experiments, we have established that knocking out DISC1 inhibits the polymerization of actin filaments at the synapse. We also identified the actin-binding protein Girdin as a potential effector to actin-based functions of DISC1 at the synapse. We establish that Girdin is expressed at the immunological synapse and that Girdin knockout cell lines showed no detectable actin at the synapse, similar to DISC1 knockouts. Using immunoprecipitation techniques, we also show that DISC1 forms a complex with Girdin in Jurkat cells. Together, these experiments suggest that DISC1 plays a role in actin signaling at the synapse through interactions with Girdin.

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