Lymphocyte Polarization During Immune Synapse Assembly: Centrosomal Actin Joins the Game

Abstract

Interactions among immune cells are essential for the development of adaptive immune responses. The immunological synapse (IS) provides a specialized platform for integration of signals and intercellular communication between T lymphocytes and antigen presenting cells (APCs). In the T cell the reorganization of surface molecules at the synaptic interface is initiated by T cell receptor binding to a cognate peptide-major histocompatibility complex on the APC surface and is accompanied by a polarized remodelling of the cytoskeleton and centrosome reorientation to a subsynaptic position. Although there is a general agreement on polarizing signals and mechanisms driving centrosome reorientation during IS assembly, the primary events that prepare for centrosome repositioning remain largely unexplored. It has been recently shown that in resting lymphocytes a local polymerization of filamentous actin (F-actin) at the centrosome contributes to anchoring this organelle to the nucleus. During early stages of IS formation centrosomal F-actin undergoes depletion, allowing for centrosome detachment from the nucleus and its polarization towards the synaptic membrane. We recently demonstrated that in CD4+ T cells the reduction in centrosomal F-actin relies on the activity of a centrosome-associated proteasome and implicated the ciliopathy-related Bardet-Biedl syndrome 1 protein in the dynein-dependent recruitment of the proteasome 19S regulatory subunit to the centrosome. In this short review we will feature our recent findings that collectively provide a new function for BBS proteins and the proteasome in actin dynamics, centrosome polarization and T cell activation.

HLA DQ protein changes the cell surface distribution pattern of HLA proteins as monitored by Förster resonance energy transfer and high‐resolution electron microscopy

“…It has been reported that membrane proteins of immune synapses localize in lipid rafts, and the appearance of a newly synthesized protein in the membrane tends to strongly affect not only the distribution and localization of other proteins but also their association with each other [34, 35]. We hypothesize that the inclusion of HLA‐DQ6 in the membrane of the cells will influence the distribution of nearby molecules such as HLA I and ICAM‐1 molecules since they are often found in immune synapses.…”

“…In soluble MHC:peptide multimer (dimers, trimers, and tetramers) experiments, the aggregation of MHC molecules can significantly increase the efficiency of the response in T cells. Several recent publications have reported on the location of immunological synapse molecules according to a certain order (organizing into "supramolecular" clusters) [35,[43][44][45][46][47][48][49]. In light of these facts, we can presume that some of the reviewed associates (e.g., the homoassociation; the HLA class II-HLA class I and the ICAM-1-HLA class I or class II heteroassociation) play a role in the process of antigen presentation and in regulating its efficiency.…”

Formin-like 1 β phosphorylation at S1086 is necessary for secretory polarized traffic of exosomes at the immune synapse

“…(3) (26) (65) (66). Thus, TCR-controlled, PKCδ-induced paxillin phosphorylation at T538 could be the above-mentioned additional PKCδ-controlled pathway not involving FMNL1β phosphorylation that may collaborate with phosphorylated FMNL1β in 20 MTOC polarization.…”

Comprehensive analysis indicated that NDE1 is a potential biomarker for pan‐cancer and promotes bladder cancer progression

“…Cytoplasmic dynein‐1 (dynein) is involved in a diverse array of functions, such as intracellular transportation of cargo, construction of the spindle apparatus and modulation of several physiological and pathological processes. These processes include cell proliferation, cell cycle regulation, signal transduction, inflammatory response and immunological response 1,2 . The predominant emphasis of previous studies investigating the relationship between abnormal regulation of dynein activity and pathological situations has mostly centred on neurodegenerative illnesses, such as Parkinson's syndrome 3 .…”