研究人员重点揭示了轴突初段（AIS）中的网格蛋白包被结构和内吞作用，以及它们与沿轴突质膜排列的周期性肌动蛋白-血影蛋白骨架的关系。通过对培养神经元进行超分辨率显微镜和电子显微镜联合观察，研究人员发现AIS中的网格蛋白包被窝位于“空白区”，这些区域缺乏肌动蛋白-血影蛋白网。
肌动蛋白-血影蛋白骨架的解组增加了网格蛋白包被窝的形成。货物摄取和活细胞成像显示，AIS中的网格蛋白包被窝特别稳定。神经元可塑性诱导刺激通过在网格蛋白包被窝周围聚合分支肌动蛋白触发了这些窝的内化。因此，血影蛋白和肌动蛋白调节网格蛋白包被窝的形成和分裂，以控制AIS处的内吞作用。
研究人员表示，网格蛋白介导的内吞作用在神经元树突和突触前区具有特征性特征，但膜蛋白如何沿轴突轴心被内化仍不清楚。
附：英文原文
Title: The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons
Author: Florian Wernert, Satish Babu Moparthi, Florence Pelletier, Jeanne Lainé, Eline Simons, Gilles Moulay, Fanny Rueda, Nicolas Jullien, Sofia Benkhelifa-Ziyyat, Marie-Jeanne Papandréou, Christophe Leterrier, Stéphane Vassilopoulos
Issue&Volume: 2024-08-23
Abstract: Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution microscopy and platinum-replica electron microscopy on cultured neurons revealed that AIS clathrin-coated pits form within “clearings”, circular areas devoid of actin-spectrin mesh. Actin-spectrin scaffold disorganization increased clathrin-coated pit formation. Cargo uptake and live-cell imaging showed that AIS clathrin-coated pits are particularly stable. Neuronal plasticity-inducing stimulation triggered internalization of the clathrin-coated pits through polymerization of branched actin around them. Thus, spectrin and actin regulate clathrin-coated pit formation and scission to control endocytosis at the AIS.
DOI: ado2032
Source: https://www.science.org/doi/10.1126/science.ado2032