Signaling at neuro/immune synapses
Michael L. Dustin
Michael L. Dustin
Published April 2, 2012
Citation Information: J Clin Invest. 2012;122(4):1149-1155. https://doi.org/10.1172/JCI58705.
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Signaling at neuro/immune synapses

Abstract

Immunological and neural synapses share properties such as the synaptic cleft, adhesion molecules, stability, and polarity. However, the mismatch in scale has limited the utility of these comparisons. The discovery of phosphatase micro-exclusion from signaling elements in immunological synapses and innate phagocytic synapses define a common functional unit at a common sub-micron scale across synapse types. Bundling of information from multiple antigen receptor microclusters by an immunological synapse has parallels to bundling of multiple synaptic inputs into a single axonal output by neurons, allowing integration and coincidence detection. Bonafide neuroimmune synapses control the inflammatory reflex. A better understanding of the shared mechanisms between immunological and neural synapses could aid in the development of new therapeutic modalities for immunological, neurological, and neuroimmunological disorders alike.

Authors

Michael L. Dustin

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Figure 1

Role of submicron receptor complexes in immunological and neural synapses.

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Role of submicron receptor complexes in immunological and neural synapse...
(A) Phagocytosis is triggered when CD45 and CD148 are excluded from a region more than 0.5 μm in diameter in which Syk is phosphorylated. (B) Micrograph of a phagocytic synapse. Scale bar: 4 μm. Arrow indicates the exclusion zone. Reproduced with permission from Nature (7). (C) T cell synapses are larger interfaces in which TCR microclusters that exclude CD45 are formed. These are linked by mysosin II–based contractility to augment signaling and trigger effector functions. Linkage of microclusters through myosin II ensures that T cells respond to multiple coincident MHC-peptide signals. Inset: TCR/MHC-peptide interactions with the support of adhesion molecules form microclusters that exclude CD45 and trigger robust tyrosine phosphorylation. TCR microclusters are short lived. (D) Micrograph of a T cell synapse. Scale bar: 4 μm. Arrow points to an example of a microcluster. Reproduced with permission from Nature (10). (E) Neural synapses are stabilized by adhesion molecules and can recruit receptor tyrosine kinases. More restrained signaling may promote a longer-lived junction than can then be used to process action potentials into chemical synapse and compute one output from many inputs. Eph, Eph family tyrosine kinase; PTP, protein tyrosine phosphatase; NT, neurotransmitter. (F) Microgaph of a neural synapse. Green indicates receptor-type protein tyrosine phosphatase ρ, red indicates neuroligin, blue indicates PSD-95. Scale bar: 4 μm. Arrows indicate examples of RPTPρ colocalization with neuroligin. Reproduced with permission from EMBO Journal (43).