Rudenko Gabby
Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, 301 University Boulevard Rm. 5.114B, Galveston, TX 77555, USA.
Neural Plast. 2017;2017:6526151. doi: 10.1155/2017/6526151. Epub 2017 Jan 31.
Synapses play a critical role in establishing and maintaining neural circuits, permitting targeted information transfer throughout the brain. A large portfolio of synaptic adhesion/organizing molecules (SAMs) exists in the mammalian brain involved in synapse development and maintenance. SAMs bind protein partners, forming -complexes spanning the synaptic cleft or -complexes attached to the same synaptic membrane. SAMs play key roles in cell adhesion and in organizing protein interaction networks; they can also provide mechanisms of recognition, generate scaffolds onto which partners can dock, and likely take part in signaling processes as well. SAMs are regulated through a portfolio of different mechanisms that affect their protein levels, precise localization, stability, and the availability of their partners at synapses. Interaction of SAMs with their partners can further be strengthened or weakened through alternative splicing, competing protein partners, ectodomain shedding, or astrocytically secreted factors. Given that numerous SAMs appear altered by synaptic activity, in vivo, these molecules may be used to dynamically scale up or scale down synaptic communication. Many SAMs, including neurexins, neuroligins, cadherins, and contactins, are now implicated in neuropsychiatric and neurodevelopmental diseases, such as autism spectrum disorder, schizophrenia, and bipolar disorder and studying their molecular mechanisms holds promise for developing novel therapeutics.
突触在建立和维持神经回路中起着关键作用，使信息能够在整个大脑中定向传递。哺乳动物大脑中存在大量参与突触发育和维持的突触粘附/组织分子（SAMs）。SAMs与蛋白质伴侣结合，形成跨越突触间隙的复合物或附着于同一突触膜的复合物。SAMs在细胞粘附和组织蛋白质相互作用网络中发挥关键作用；它们还可以提供识别机制，生成伴侣可以停靠的支架，并且可能也参与信号传导过程。SAMs通过一系列不同机制进行调节，这些机制会影响它们的蛋白质水平、精确定位、稳定性以及它们在突触处伴侣的可用性。SAMs与其伴侣之间的相互作用可以通过可变剪接、竞争性蛋白质伴侣、胞外域脱落或星形胶质细胞分泌因子进一步增强或减弱。鉴于许多SAMs在体内似乎会因突触活动而发生改变，这些分子可能用于动态增强或减弱突触通讯。许多SAMs，包括神经连接蛋白、神经配体、钙黏蛋白和接触蛋白，现在都与神经精神疾病和神经发育疾病有关，如自闭症谱系障碍、精神分裂症和双相情感障碍，研究它们的分子机制有望开发出新的治疗方法。
