单个神经元的轴突-树突和顶点-基底外侧分选

IF 3.3 3区 生物学
Genetics Pub Date : 2022-05-05 DOI:10.1093/genetics/iyac036
Monique Lillis, Nathan J Zaccardi, Maxwell G Heiman
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引用次数: 0

摘要

摘要细胞是高度组织化的机器,具有功能专门的隔间。例如,膜蛋白定位于神经元中的轴突或树突,以及上皮细胞中的顶端或基底外侧表面。有趣的是,许多感觉细胞——包括脊椎动物的感光细胞和嗅觉神经元——同时表现出神经元和上皮细胞的特征。在这里,我们发现秀丽隐杆线虫的两个神经元同时表现出像神经元一样的轴突树突分类和像上皮细胞一样的顶端基底外侧分类。树突的远端~5–10µm为顶端,而树突、胞体和轴突的其余部分为基底外侧。为了确定蛋白质是如何在这些区室中分类的,我们研究了保守的粘附分子SAX-7/L1CAM的定位。使用最小合成的跨膜蛋白,我们发现SAX-7的91个氨基酸的细胞质尾部对于指导基底外侧定位是必要的和充分的。可以使用2个短(10aa或19aa)尾序列中的任一个来完全概括基底外侧定位,该序列分别类似于已知在哺乳动物上皮中介导分选的基于二亮氨酸和Tyr的基序。基于Tyr的基序在人类L1CAM中是保守的,但以前没有被赋予功能。破坏任一序列中的关键残基会导致顶端定位,而“改进”它们以匹配上皮分选基序会导致仅轴突定位。事实上,在一个短基序中仅改变2个残基就足以在顶端、基底外侧和轴突定位之间重定向蛋白质。我们的研究结果表明,轴突树突和顶端基底外侧分选途径可以共存于一个细胞中,并表明短序列基序的细微变化足以在这些途径之间重定向蛋白质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Axon-dendrite and apical-basolateral sorting in a single neuron.

Cells are highly organized machines with functionally specialized compartments. For example, membrane proteins are localized to axons or dendrites in neurons and to apical or basolateral surfaces in epithelial cells. Interestingly, many sensory cells-including vertebrate photoreceptors and olfactory neurons-exhibit both neuronal and epithelial features. Here, we show that Caenorhabditis elegans amphid neurons simultaneously exhibit axon-dendrite sorting like a neuron and apical-basolateral sorting like an epithelial cell. The distal ∼5-10 µm of the dendrite is apical, while the remainder of the dendrite, soma, and axon are basolateral. To determine how proteins are sorted among these compartments, we studied the localization of the conserved adhesion molecule SAX-7/L1CAM. Using minimal synthetic transmembrane proteins, we found that the 91-aa cytoplasmic tail of SAX-7 is necessary and sufficient to direct basolateral localization. Basolateral localization can be fully recapitulated using either of 2 short (10-aa or 19-aa) tail sequences that, respectively, resemble dileucine and Tyr-based motifs known to mediate sorting in mammalian epithelia. The Tyr-based motif is conserved in human L1CAM but had not previously been assigned a function. Disrupting key residues in either sequence leads to apical localization, while "improving" them to match epithelial sorting motifs leads to axon-only localization. Indeed, changing only 2 residues in a short motif is sufficient to redirect the protein between apical, basolateral, and axonal localization. Our results demonstrate that axon-dendrite and apical-basolateral sorting pathways can coexist in a single cell, and suggest that subtle changes to short sequence motifs are sufficient to redirect proteins between these pathways.

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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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