Immune Netw.  2012 Jun;12(3):71-83. 10.4110/in.2012.12.3.71.

Actin Engine in Immunological Synapse

• Piragyte I
• Jun CD

• KMID: 2168004
• DOI: http://doi.org/10.4110/in.2012.12.3.71

Abstract

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.

Keyword

Actin; Immunological synapse; Regulation; T cells

MeSH Terms

Actin Cytoskeleton
Actins
Antigen-Presenting Cells
Biophysics
Immune System
Immunological Synapses
Microscopy
T-Lymphocytes
Ursidae
Actins

Figure

• 

  Figure 1 T cell and APC interaction stages. (A) In the first stage, T cells scan APC surface for specific peptide loaded on MHC class molecule. (B) Once CD4+ T cell find a specific MHCp, pseudopodia-like structures are established. T cell starts to polarize. (C) Immunological synapse is formed and sustained; centrioles are translocated proximally to IS. (D) Termination of immunological synapse; organelles lose their polarity.

• 

  Figure 2 Main proteins that mediate actin cytoskeleton rearrangement in IS. (A) T cells express mDIA1, which can bind to profilin - actin nucleating protein. mDia1 participates in unbranched nucleation of actin filaments independently from Arp2/3 complex. (B) HS1 colocalizes with Arp2/3 complex, thereby increasing the rate of actin assembly and promoting branched actin network formation induced by Arp2/3. (C) WASp family proteins through VCA domain in C-terminus bind complexes formed from Arp2 and Arp3. Activated Arp2/3 complexes then recruit monomeric actins, and promote nucleation of branched actin filaments. (D) Arp2/3 complex is known to have actin nucleating activity and ability to organize actin filaments into branched networks. Arp2 and Arp3 are structurally similar to actin. (E) Actin depolymerization occurs passively in the ageing end of actin filament and is regulated by ADF and cofilins. (F) L-plastin has two sites for actin binding; therefore, it can aggregate actin filaments into parallel bundles.

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