Stryker Emily, Johnson Karl G
Department of Biology and Program in Neuroscience, Pomona College, 175 West 6th Street, Claremont, CA 91711, USA.
J Cell Sci. 2007 Nov 1;120(Pt 21):3723-8. doi: 10.1242/jcs.03491.
Active zones are protein-rich regions of neurons that act as sites of synaptic vesicle fusion and neurotransmitter release at the pre-synaptic terminus. Although the discovery that the receptor protein tyrosine phosphatase LAR and its cytoplasmic binding partner liprin alpha are essential for proper active zone formation is nearly a decade old, the underlying mechanisms are still poorly understood. Recent studies have identified a number of binding partners for both LAR and liprin alpha, several of which play key roles in active zone assembly. These include nidogen, dallylike and syndecan--extracellular ligands for LAR that regulate synapse morphogenesis. In addition, liprin-alpha-interacting proteins such as ERC2, RIM and the MALS/Veli-Cask-Mint1 complex cooperate to form a dense molecular scaffold at the active zone that is crucial for proper synaptic function. These studies allow us to propose testable models of LAR and liprin alpha function, and provide insights into the fundamental molecular mechanisms of synapse formation and stabilization.
活性区是神经元中富含蛋白质的区域，在突触前末梢充当突触小泡融合和神经递质释放的位点。尽管受体蛋白酪氨酸磷酸酶LAR及其胞质结合伴侣liprin alpha对正常活性区形成至关重要这一发现已有近十年时间，但其潜在机制仍知之甚少。最近的研究确定了LAR和liprin alpha的许多结合伴侣，其中一些在活性区组装中起关键作用。这些包括巢蛋白、类达利蛋白和多配体蛋白聚糖——LAR的细胞外配体，可调节突触形态发生。此外，与liprin-alpha相互作用的蛋白，如ERC2、RIM和MALS/Veli-Cask-Mint1复合物，协同在活性区形成致密的分子支架，这对正常的突触功能至关重要。这些研究使我们能够提出关于LAR和liprin alpha功能的可测试模型，并深入了解突触形成和稳定的基本分子机制。
