Bloom Ona, Unternaehrer Julia J, Jiang Aimin, Shin Jeong-Sook, Delamarre Lélia, Allen Patrick, Mellman Ira
Department of Cell Biology, Ludwig Institute for Cancer Research, New Haven, CT 06520, USA.
J Cell Biol. 2008 Apr 21;181(2):203-11. doi: 10.1083/jcb.200711149. Epub 2008 Apr 14.
The adaptive immune response is initiated by the presentation of peptides bound to major histocompatibility complex molecules on dendritic cells (DCs) to antigen-specific T lymphocytes at a junction termed the immunological synapse. Although much attention has been paid to cytoplasmic events on the T cell side of the synapse, little is known concerning events on the DC side. We have sought signal transduction components of the neuronal synapse that were also expressed by DCs. One such protein is spinophilin, a scaffolding protein of neuronal dendritic spines that regulates synaptic transmission. In inactive, immature DCs, spinophilin is located throughout the cytoplasm but redistributes to the plasma membrane upon stimulus-induced maturation. In DCs interacting with T cells, spinophilin is polarized dynamically to contact sites in an antigen-dependent manner. It is also required for optimal T cell activation because DCs derived from mice lacking spinophilin exhibit defects in antigen presentation both in vitro and in vivo. Thus, spinophilin may play analogous roles in information transfer at both neuronal and immunological synapses.
适应性免疫反应是由树突状细胞(DCs)上与主要组织相容性复合体分子结合的肽段在一个称为免疫突触的连接处呈递给抗原特异性T淋巴细胞而启动的。尽管人们对突触T细胞一侧的胞质事件给予了很多关注,但对于DCs一侧的事件却知之甚少。我们寻找了也由DCs表达的神经元突触的信号转导成分。其中一种蛋白质是亲嗜素,它是神经元树突棘的一种支架蛋白,可调节突触传递。在无活性的未成熟DCs中,亲嗜素位于整个细胞质中,但在刺激诱导的成熟过程中会重新分布到质膜上。在与T细胞相互作用的DCs中,亲嗜素以抗原依赖的方式动态极化到接触部位。它也是最佳T细胞活化所必需的,因为源自缺乏亲嗜素的小鼠的DCs在体外和体内的抗原呈递中都表现出缺陷。因此,亲嗜素可能在神经元和免疫突触的信息传递中发挥类似作用。