Kaeser Pascal S
Stanford Institute for Neuro-Innovation & Translational Neurosciences; Department of Molecular and Cellular Physiology; Stanford University; Stanford, CA USA.
Cell Logist. 2011 May;1(3):106-110. doi: 10.4161/cl.1.3.16429.
In a presynaptic nerve terminal, neurotransmitter release is largely restricted to specialized sites called active zones. Active zones consist of a complex protein network, and they organize fusion of synaptic vesicles with the presynaptic plasma membrane in response to action potentials. Rab3-interacting molecules (RIMs) are central components of active zones. In a recent series of experiments, we have systematically dissected the molecular mechanisms by which RIMs operate in synaptic vesicle release. We found that RIMs execute two critical functions of active zones by virtue of independent protein domains. They tether presyanptic Ca(2+) channels to the active zone, and they activate priming of synaptic vesicles by monomerizing homodimeric, constitutively inactive Munc13. These data indicate that RIMs orchestrate synaptic vesicle release into a coherent process. In conjunction with previous studies, they suggest that RIMs form a molecular platform on which plasticity of synaptic vesicle release can operate.
在突触前神经末梢，神经递质的释放主要局限于称为活性区的特化部位。活性区由一个复杂的蛋白质网络组成，它们响应动作电位来组织突触小泡与突触前质膜的融合。Rab3相互作用分子（RIMs）是活性区的核心成分。在最近一系列实验中，我们系统地剖析了RIMs在突触小泡释放中发挥作用的分子机制。我们发现，RIMs凭借独立的蛋白质结构域执行活性区的两个关键功能。它们将突触前Ca(2+)通道拴系到活性区，并通过使同型二聚体、组成型无活性的Munc13单体化来激活突触小泡的引发。这些数据表明，RIMs将突触小泡释放协调成一个连贯的过程。结合先前的研究，这些数据提示RIMs形成了一个分子平台，突触小泡释放的可塑性可在该平台上发挥作用。
