Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
Neuron. 2011 May 12;70(3):441-54. doi: 10.1016/j.neuron.2011.03.022.
Proteins vital to presynaptic function are synthesized in the neuronal perikarya and delivered into synapses via two modes of axonal transport. While membrane-anchoring proteins are conveyed in fast axonal transport via motor-driven vesicles, cytosolic proteins travel in slow axonal transport via mechanisms that are poorly understood. We found that in cultured axons, populations of cytosolic proteins tagged to photoactivatable GFP (PAGFP) move with a slow motor-dependent anterograde bias distinct from both vesicular trafficking and diffusion of untagged PAGFP. The overall bias is likely generated by an intricate particle kinetics involving transient assembly and short-range vectorial spurts. In vivo biochemical studies reveal that cytosolic proteins are organized into higher order structures within axon-enriched fractions that are largely segregated from vesicles. Data-driven biophysical modeling best predicts a scenario where soluble molecules dynamically assemble into mobile supramolecular structures. We propose a model where cytosolic proteins are transported by dynamically assembling into multiprotein complexes that are directly/indirectly conveyed by motors.
对突触前功能至关重要的蛋白质是在神经元胞体中合成的，并通过两种轴突运输模式被输送到突触中。虽然膜锚定蛋白通过马达驱动的囊泡在快速轴突运输中传递，但细胞质蛋白通过机制较差的缓慢轴突运输进行运输。我们发现，在培养的轴突中，标记有光活化 GFP（PAGFP）的细胞质蛋白群体以与囊泡运输和未标记 PAGFP 的扩散不同的慢马达依赖的顺行偏倚移动。整体偏倚可能是由涉及短暂组装和短程向量迸发的复杂粒子动力学产生的。体内生化研究表明，细胞质蛋白在富含轴突的部分中组织成更高阶的结构，这些结构在很大程度上与囊泡分离。数据驱动的生物物理模型最好预测了一种情景，即可溶性分子动态组装成可移动的超分子结构。我们提出了一种模型，其中细胞质蛋白通过动态组装成多蛋白复合物来运输，这些复合物直接/间接由马达传递。
