Neuronal and Immune Synapses on the Move at Traffic

Traffic celebrates the synapse with a series of reviews titled “Neurological and Immune Synapses in Health and Disease”. These reviews discuss novel findings that highlight the ever-increasing complexity and dynamic character of both neuronal and immune synapses. Neuronal synapses are defined as specialized, discrete and closely apposed zones of communication between excitable cells (1,2). Here we focus on chemical synapses where cell communication occurs without cytoplasmic continuity. Similar to the chemical synapse, immune synapses are specialized zones of communication between a T or B lymphocyte and an antigen-presenting cell or antibody-bound antigen, respectively. In his 1999 definition of an immune synapse, Michael L. Dustin emphasized the supramolecular organization and domain segregation at a contact site between lymphocytes and antigen-presenting cells as a necessary step for cell–cell communication and lymphocyte activation (3,4). Dustin underlined that the immune synapse ‘consists of a central cluster of T cell receptors surrounded by a ring of adhesion molecules’ (3). This supramolecular organization of the immune synapse inspired the exploration of the neuronal synapse by Roos and Kelly, who presented some of the first evidence of supramolecular organization and domain segregation in the neuronal synapse (5). The goal of this review series is to create a platform for idea cross-fertilization where concepts borne out of one field stimulate experimentally testable ideas in the other field. For example, the Crawford and Kavalali review suggest the concept that there may be more than one functional synapse within what we nowadays consider a single neuronal synapse unit, as they discuss the molecular diversity of synaptic vesicles within a synapse. Additionally, another review by Finetti, Onnis and Baldari explores intraflagellar transport (IFT) mechanisms setting up polarized immune synapses. These concepts have no precedent, thus opening doors for potentially novel hypotheses and fresh experimentation in multiple experimental systems. Since its inception in 1897, the concept of the synapse has proven its utility by creating a link between the structural and physiological views of the contact points between neurons emerging from the works of Cajal and Sherrington, respectively (6). The synapse remains a viable concept both in neuroscience and immunology because it continues to synthesize the ever-expanding and dynamic molecular anatomy of these cell–cell contacts (7–9). It is quite telling that dynamicity, as in ‘amoeboid’ cell contacts, was a centerpiece at the birth of the synapse concept by Sherrington (10,11):