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Spinophilin and the immune synapse.

Seed B, Xavier R - J. Cell Biol. (2008)

Bottom Line: Now, equally if not more dramatic changes are found to take place in cells presenting an antigen.Delamarre, P.Mellman. 2008.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. bseed@ccib.mgh.harvard.edu

ABSTRACT
Extensive alterations in cellular organization are known to accompany the responses of sensitized T cells to target cells presenting an antigen of interest. Now, equally if not more dramatic changes are found to take place in cells presenting an antigen. With the help of a spinophilin-GFP fusion protein, Bloom et al. (Bloom, O., J.J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman. 2008. J. Cell Biol. 181:203-211) have captured a remarkable polarization of the cellular architecture of dendritic cells presenting an antigen to T cells.

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Related in: MedlinePlus

Opportunities to mine the neuronal synaptic proteome for molecules of relevance to the immune synapse. (A) Schematic diagram of the interaction between a T cell and a dendritic cell that is presenting an antigen. When T cells encounter antigen-presenting cells, sequential recruitment of adhesion molecules and cytoplasmic signaling molecules contribute to the local assembly of the immune synapse. The adaptor protein spinophilin bears PDZ and actin-binding domains that allow it to undergo relocalization, presumably to engage or convey important client proteins, in the formation of the immune synapse. (B) Relative mRNA expression levels of proteins containing PDZ domains (candidate scaffold/adaptor proteins) that are differentially distributed between lymphocytes and dendritic cells.
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fig1: Opportunities to mine the neuronal synaptic proteome for molecules of relevance to the immune synapse. (A) Schematic diagram of the interaction between a T cell and a dendritic cell that is presenting an antigen. When T cells encounter antigen-presenting cells, sequential recruitment of adhesion molecules and cytoplasmic signaling molecules contribute to the local assembly of the immune synapse. The adaptor protein spinophilin bears PDZ and actin-binding domains that allow it to undergo relocalization, presumably to engage or convey important client proteins, in the formation of the immune synapse. (B) Relative mRNA expression levels of proteins containing PDZ domains (candidate scaffold/adaptor proteins) that are differentially distributed between lymphocytes and dendritic cells.

Mentions: By a conspiracy of terminology, the most effective antigen-presenting cells in the immune system are known as dendritic cells for their extensively arborized structures. After the pioneering efforts of Steinman and Cohn (1974) brought their unusual potency to light, dendritic cells became of considerable interest to immunologists and were found to exhibit a rich biology that enables the organism to sensitively respond to changes in the environment that herald the presence of pathogens (Steinman, 2007). Bloom et al. (2008) vividly document here the participation of dendritic cell spinophilin in antigen presentation through a variety of microscopic studies that illustrate dramatic changes in spinophilin distribution accompanying the formation of the immunological synapse. Although the impact of the spinophilin phenotype on the extent of activation in the examples presented in this study is not as spectacular as the visible manifestation of cytostructural reorganization, the impact on activation is well documented and clearly points to a function for spinophilin in the creation of a highly effective immune response. In some ways, this is reminiscent of but not perfectly congruent with the behavior of another protein borrowed from the central nervous system by dendritic cells, plexin-A1. Plexins constitute a family of cell surface proteins that are known to act as receptors for semaphorins. In dendritic cells, plexin-A1 appears to be retained in an intracellular, presumably vesicular, compartment, making its way to the cell surface after TNFα stimulation, where it clusters in a multifocal pattern localizing to the T cell synapse (Fig. 1 A; Eun et al., 2006). The mechanism that controls this behavior, like that of spinophilin, is not well understood.


Spinophilin and the immune synapse.

Seed B, Xavier R - J. Cell Biol. (2008)

Opportunities to mine the neuronal synaptic proteome for molecules of relevance to the immune synapse. (A) Schematic diagram of the interaction between a T cell and a dendritic cell that is presenting an antigen. When T cells encounter antigen-presenting cells, sequential recruitment of adhesion molecules and cytoplasmic signaling molecules contribute to the local assembly of the immune synapse. The adaptor protein spinophilin bears PDZ and actin-binding domains that allow it to undergo relocalization, presumably to engage or convey important client proteins, in the formation of the immune synapse. (B) Relative mRNA expression levels of proteins containing PDZ domains (candidate scaffold/adaptor proteins) that are differentially distributed between lymphocytes and dendritic cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2315665&req=5

fig1: Opportunities to mine the neuronal synaptic proteome for molecules of relevance to the immune synapse. (A) Schematic diagram of the interaction between a T cell and a dendritic cell that is presenting an antigen. When T cells encounter antigen-presenting cells, sequential recruitment of adhesion molecules and cytoplasmic signaling molecules contribute to the local assembly of the immune synapse. The adaptor protein spinophilin bears PDZ and actin-binding domains that allow it to undergo relocalization, presumably to engage or convey important client proteins, in the formation of the immune synapse. (B) Relative mRNA expression levels of proteins containing PDZ domains (candidate scaffold/adaptor proteins) that are differentially distributed between lymphocytes and dendritic cells.
Mentions: By a conspiracy of terminology, the most effective antigen-presenting cells in the immune system are known as dendritic cells for their extensively arborized structures. After the pioneering efforts of Steinman and Cohn (1974) brought their unusual potency to light, dendritic cells became of considerable interest to immunologists and were found to exhibit a rich biology that enables the organism to sensitively respond to changes in the environment that herald the presence of pathogens (Steinman, 2007). Bloom et al. (2008) vividly document here the participation of dendritic cell spinophilin in antigen presentation through a variety of microscopic studies that illustrate dramatic changes in spinophilin distribution accompanying the formation of the immunological synapse. Although the impact of the spinophilin phenotype on the extent of activation in the examples presented in this study is not as spectacular as the visible manifestation of cytostructural reorganization, the impact on activation is well documented and clearly points to a function for spinophilin in the creation of a highly effective immune response. In some ways, this is reminiscent of but not perfectly congruent with the behavior of another protein borrowed from the central nervous system by dendritic cells, plexin-A1. Plexins constitute a family of cell surface proteins that are known to act as receptors for semaphorins. In dendritic cells, plexin-A1 appears to be retained in an intracellular, presumably vesicular, compartment, making its way to the cell surface after TNFα stimulation, where it clusters in a multifocal pattern localizing to the T cell synapse (Fig. 1 A; Eun et al., 2006). The mechanism that controls this behavior, like that of spinophilin, is not well understood.

Bottom Line: Now, equally if not more dramatic changes are found to take place in cells presenting an antigen.Delamarre, P.Mellman. 2008.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA. bseed@ccib.mgh.harvard.edu

ABSTRACT
Extensive alterations in cellular organization are known to accompany the responses of sensitized T cells to target cells presenting an antigen of interest. Now, equally if not more dramatic changes are found to take place in cells presenting an antigen. With the help of a spinophilin-GFP fusion protein, Bloom et al. (Bloom, O., J.J. Unternaehrer, A. Jiang, J.-S. Shin, L. Delamarre, P. Allen, and I. Mellman. 2008. J. Cell Biol. 181:203-211) have captured a remarkable polarization of the cellular architecture of dendritic cells presenting an antigen to T cells.

Show MeSH
Related in: MedlinePlus