美国斯坦福大学Kang Shen团队发现，轴突起始段的内吞作用维持神经元的极性。该项研究成果于2022年8月17日在线发表在《自然》杂志上。
研究人员发现在线虫、小鼠、大鼠和人类神经元中，树突和轴突极化的跨膜蛋白被轴突起始段（AIS）中的内吞机器识别，被强力内吞并被定向到晚期内体降解。迫使受体与AIS主要组织者ankyrinG相互作用可拮抗受体在AIS中的内吞作用，导致受体在AIS中的积累，并导致极性缺陷，随后出现形态学和行为学缺陷。因此，内吞的清除扩散到AIS的极性受体是一种膜清除机制，可能与已知的AIS扩散屏障机制共同作用，从而维持质膜上的神经元极性。这些研究结果揭示了AIS中一个保守的內吞清除机制，通过加强轴突和树突隔层的膜边界来维持神经元的极性。
据悉，神经元是高度极化的细胞，它面临着将大量不同的蛋白质分门别类的基本挑战，以便正常运作。AIS是一个专门的区域，它将神经元的形态、生化和功能上不同的轴突和树突隔开。AIS是如何在这些区室之间保持极性的，目前尚不完全清楚。
附：英文原文
Title: Endocytosis in the axon initial segment maintains neuronal polarity
Author: Eichel, Kelsie, Uenaka, Takeshi, Belapurkar, Vivek, Lu, Rui, Cheng, Shouqiang, Pak, Joseph S., Taylor, Caitlin A., Sdhof, Thomas C., Malenka, Robert, Wernig, Marius, zkan, Engin, Perrais, David, Shen, Kang
Issue&Volume: 2022-08-17
Abstract: Neurons are highly polarized cells that face the fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly1. The axon initial segment (AIS) is a specialized domain that separates a neuron’s morphologically, biochemically and functionally distinct axon and dendrite compartments2,3. How the AIS maintains polarity between these compartments is not fully understood. Here we find that in Caenorhabditis elegans, mouse, rat and human neurons, dendritically and axonally polarized transmembrane proteins are recognized by endocytic machinery in the AIS, robustly endocytosed and targeted to late endosomes for degradation. Forcing receptor interaction with the AIS master organizer, ankyrinG, antagonizes receptor endocytosis in the AIS, causes receptor accumulation in the AIS, and leads to polarity deficits with subsequent morphological and behavioural defects. Therefore, endocytic removal of polarized receptors that diffuse into the AIS serves as a membrane-clearance mechanism that is likely to work in conjunction with the known AIS diffusion-barrier mechanism to maintain neuronal polarity on the plasma membrane. Our results reveal a conserved endocytic clearance mechanism in the AIS to maintain neuronal polarity by reinforcing axonal and dendritic compartment membrane boundaries.
DOI: 10.1038/s41586-022-05074-5
Source: https://www.nature.com/articles/s41586-022-05074-5
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
