内容来源：https://www.quantamagazine.org/disorder-drives-one-of-natures-most-complex-machines-20260309/

内容总结：

生命核心“守门员”真容初现：无序运动竟是细胞核孔关键机制

在真核细胞的核心——细胞核表面，分布着一些精妙而复杂的结构：核孔复合体。它们犹如细胞核的“智能海关”，每秒指挥成百上千个分子有序进出，严格控制着蛋白质合成、基因调控等生命活动。然而，这个由数百个蛋白质构成、拥有八重对称花瓣状结构的巨型分子机器，其核心筛选机制数十年来始终成谜。

近日，一项发表于《自然·细胞生物学》的研究，通过高速原子力显微镜首次以毫秒级分辨率捕捉到了核孔复合体中央运输通道的动态变化。研究团队发现，通道中心存在一个由转运蛋白及其携带的“货物”分子构成的、不断移动和重组的“中央栓”。这个动态结构并非固定障碍，而是像拥挤舞池中熟练的舞者：能与转运蛋白正确结合的分子被快速接力传送通过；而无序闯入者则被推离。

这一发现挑战了以往关于通道内部是静态“凝胶”还是“刷状”结构的争论，支持了一种更动态的“虚拟门”模型。核孔的核心功能似乎并非依赖于有序排列，而是由内在无序蛋白质（FG-核孔蛋白）的快速波动和动态相互作用所驱动。“是‘无序’而非‘有序’产生了这一功能，”研究人员指出。

核孔复合体的功能至关重要，其异常与多种疾病密切相关。研究表明，某些癌症细胞和病毒可能通过干扰核孔蛋白来劫持细胞的蛋白质合成机器或关闭免疫应答。因此，深入解析其动态工作机制，不仅有助于理解生命的基本原理，也为开发针对神经发育障碍、病毒性疾病和癌症的新疗法提供了潜在靶点。科学家们正试图通过操控这个“守门员”，以阻止病原体入侵，或引导治疗性分子进入细胞核。

随着冷冻电镜、MINFLUX超分辨成像等新技术的涌现，科学家正以前所未有的精度窥探这个生命核心门户的奥秘。尽管其内部世界的完整图景仍有待揭示，但可以肯定的是，这个看似无序的动态系统，正是细胞实现高效、精准物质运输和信息整合的关键所在。

中文翻译：

无序驱动着自然界最精密的机器之一

引言

在复杂生命诞生之初，进化创造了一个容器来存放其最珍贵的物品——DNA。数十亿年后，20世纪的显微镜学家近距离观察了这个容器——细胞核，发现其表面布满了微小的孔洞。当时，他们并不清楚这些结构的用途，但随着显微技术的进步，一个宏伟的景象逐渐清晰起来：那就是我们现在所称的“核孔复合体”，它是迄今为止形成的最庞大、最奇妙的分子机器之一。

每个核孔复合体都由数百个蛋白质构成，这些蛋白质分属大约30种不同类型。从正面看，它像一朵八瓣花；从侧面看，则像一个飞碟。其中心开口处垂挂着许多像意大利面一样的蛋白质，它们锚定在复合体的内壁上。

“这是一件极其美丽的东西，”洛克菲勒大学的化学生物学家布莱恩·柴特说。“它很奇妙。它是一个奇迹……它非同凡响。”

这台机器肩负着一项至关重要的任务：引导分子进出细胞核。它不仅仅是一扇敞开的门，这个蛋白质复合体还能识别接近的不同分子，并且只允许其中一部分通过。“核孔复合体最终是细胞核的守门人，”瑞士巴塞尔大学的生物物理学家罗德里克·林说，“所有必须进出细胞核的物质都必须通过这些孔道。”

几乎每个真核细胞的细胞核上都布满了核孔复合体，而且复合体的主要成分在不同物种间——从单细胞酵母到多细胞的人类——都惊人地保守。进化“只发明了这东西一次，然后就一直用它了，”加州理工学院的结构细胞生物学家安德烈·霍尔茨说。

一个哺乳动物的细胞核可能包含数千个核孔复合体。每秒钟，每个核孔都会让成百上千个形状大小各异的分子通过，以便它们到达目的地去制造蛋白质、调控基因，并总体上帮助细胞运作。一些大分子由蛋白质携带通过通道，而小分子则自行扩散通过。有些分子能毫不费力地滑过，而对另一些分子来说，它却是一道无法穿透的屏障。

这扇门如何以如此高的选择性工作，一直是个谜。几十年来，生物学家已经弄清楚了这台机器大部分静态部件的模样。但其中心区域却永不停歇，不断地运动和变形，这使得即使是最好的成像方法也难以将其可视化。

这种情况正在逐渐改变。在2025年底发表于《自然·细胞生物学》的一项研究中，高分辨率显微技术以毫秒级分辨率展示了中心屏障的运动，揭示了一个不断自我重组的柔性结构。实验成像结合计算模型表明，核孔复合体的功能是由其灵活性和运动所引导的。

这不仅仅是满足学术好奇心。近期大量研究已将神经发育障碍、病毒性疾病和癌症与核孔复合体的问题联系起来。如果生物学家能够弄清楚其细胞运输系统的工作原理，他们就有可能开发出阻止有害病原体通过的方法，并尝试将治疗性分子引导至基因组所在的细胞核内。

“我们正开始接近来自不同生物的核孔的近原子级图像，”洛克菲勒大学的细胞生物学家迈克·劳特说，他领导了这项新研究，为理解真核生命核心的分子机器提供了新见解。

美丽之物

对于许多研究核孔的科学家来说，它立刻就能让人着迷：他们惊叹于这个（相对）庞大的生物机器竟然能让如此多种类、如此多数量的分子高效地进出细胞核，而且几乎不出差错。

“它很美，”霍尔茨说。“你怎么能造出一个飞机库，它的门能让一架747通过，”却不让一颗小弹珠飞出去？

不知何故，这扇门本身必须充当生命重要分子的“保镖”。RNA分子必须离开细胞核进入细胞质才能制造蛋白质。负责制造蛋白质的核糖体本身，就是由在细胞核内组装、并通过核孔运出的分子构成的。同时，参与调控基因组的分子必须优先被引导进入细胞核。在这些过程进行时，核孔也在阻挡那些不属于这里的东西，比如有害的酶或错误折叠的RNA。

在发现核孔复合体后的几十年里，生物学家利用电子显微镜、物理学工具和计算机建模，逐渐对其结构有了更深入的了解。随着冷冻电子显微镜——一种在快速冷冻细胞后进行成像的强大技术——的出现，他们得以评估机器的静态部件。这些努力已经生成了构成八个花瓣状辐射单元的每个蛋白质的近原子级视图。但这项技术对被称为运输通道的中心区域却不起作用，那里是核孔大部分活动发生的地方。

“每当有人用这些显微镜窥视核孔内部时，他们看到的只是里面一团无定形的云，”林说。“就像一层雾。”

原因在20世纪90年代变得明显：这台巨型机器的中心充满了没有明显或特定结构的蛋白质。这些被称为FG核孔蛋白的蛋白质，其尾部像海草一样摆动，无法在静态图像中被捕捉。这些尾部是“核孔复合体的暗物质”，霍尔茨说。

大多数蛋白质会折叠成特定的结构或形状，这对它们在细胞中执行的功能至关重要。但本质无序蛋白——包括这些核孔蛋白在内的一类蛋白质——没有单一的结构。它们四处摆动，改变形状并与不同的分子结合。

这意味着在核孔复合体的中心，“一切都是由无序介导的，”荷兰格罗宁根大学的计算物理学家帕特里克·昂克说。“不是有序产生了这种功能。是无序。”

21世纪初，该领域充斥着关于FG核孔蛋白在运输通道中的组织和行为，以及它们如何运输分子进出细胞核的争论。研究人员一致认为，大多数大分子如果没有被称为运输因子的载货蛋白的帮助，就无法通过通道。运输因子在通道中与核孔蛋白相互作用，只与那些包含特定短链氨基酸序列的分子结合——这个分子标签“实际上是在说，‘把我送进细胞核’，”劳特说。但研究人员对于通道本身如何组织存在分歧，这会影响到分子如何通过它。一些人认为核孔蛋白会相互结合，形成一个凝胶状的网状网络。另一些人则认为，这些无序蛋白彼此之间相互作用不多，而是像刷子上的鬃毛一样不断波动。

争论变得激烈起来。“过去常常非常敌对，”霍尔茨回忆道。“人们对自己所做的事情充满热情。这不是个人恩怨。”

“在很长一段时间里，情况就像是，‘你是凝胶派，还是刷子派？’非此即彼，”德克萨斯农工大学的细胞生物学家西格弗里德·穆瑟说。

近年来，新的合作与讨论，包括每年一次的主要研究人员聚首聊天的会议，已经平息了冲突。但关于运输通道结构和功能的真相尚未得到解决。研究人员需要更具创造力，才能理解这个复合体在其原生环境中是如何运作的。

“我们只是想回到核孔复合体本身，真正让核孔告诉我们它在做什么，”劳特说，“而不是由我们强加给它我们认为它在做什么。”

快速敲击者

如何探究一个分子复合体？劳特和林都主张一个更动态的核孔模型，他们从一个简单的想法开始：戳它。

劳特花了数十年时间研究酵母核孔复合体的特性。林是高速原子力显微镜的专家，这项技术使用一个非常尖锐的探针在表面轻轻快速地敲击，以感知其运动方式。

几年前，在一个黑暗的地下实验室里，林的研究生小斋俊也开始打开装有数百万个酵母核孔复合体的塑料小瓶。林回忆说，他在“我们系的地牢里”辛苦工作了数天，不间断地工作，以便在样品新鲜时将其放入高速原子力显微镜中。“这真是一项充满热爱的工作。”

他的努力使团队能够观察运输通道每毫秒的变化。“我们可以看到非常清晰、超快速的运动，”劳特回忆道。由此产生的视频在我们这些宏观生物看来可能很模糊，但它们是对纳米级运输通道行为的一些最高清晰度的观察。

在通道边缘靠近壁的地方，劳特和林的团队看到了分子的快速波动——那些就是摆动的核孔蛋白。在中心，他们看到了一个模糊的团块，即中央栓，它在运输通道内不断移动和重新定位。长期以来，生物学家一直怀疑可能存在一个中央栓，但在之前的显微图像中，它并不总是可见。

“眼见为实，”未参与这项研究的霍尔茨说。能够展示这一点“是一件美好的事”。

在柴特的带领下，团队利用质谱分析发现，这个栓是由称为核转运蛋白（简称“kaps”）的运输蛋白及其分子货物组成的。当kaps通过核孔时，它们会抓住核孔蛋白，将其拉向通道中心。这就形成了一个临时的、动态的障碍，减缓或阻止其他分子通过。劳特说，这样一来，kaps不仅帮助携带分子穿过，还推开了任何不应该在那里的东西。当他们加入更多的运输因子时，他们看到栓变得更大。

核孔复合体的核心正不断地被kaps重新排列，创造一个不断变化的环境。劳特说，结果表明，核孔的组织和行为比凝胶网络动态得多，更接近于刷状环境。这些发现支持了他之前提出的一个模型，称为“虚拟门”，其中环境的动态性对于引导蛋白质离开或通过至关重要。他将其比作一个拥挤的舞池。

“如果你会跳舞，你可以直接进入舞池，从一个舞伴换到另一个舞伴，手拉手，快速交换着穿过，”他说。“如果你不会跳舞，你看到的只是这场混乱的混战，而你试图加入。没有人抓住你帮你进入舞池，所以你只是被推开了。”

为了进一步验证他们的观察结果，劳特和林制造了与天然核孔复合体大小相同的合成孔。当他们在内部锚定核孔蛋白并添加运输因子后，合成孔的行为就像野生的酵母核孔复合体一样。他们看到了中央栓的出现。

“我觉得非常引人注目的是，他们用一个非常简单的模型重现了这个结果，”穆瑟说。“这是一个相当惊人的结果。”

门未关闭

霍尔茨并不完全相信这是对凝胶模型的致命一击。他说，“答案很可能在中间，这在科学中很常见。”他推测，研究人员可能捕捉到了中央通道的不同构型，因为它一直在变化，或者也许某些核孔的内部通道更像凝胶，而另一些则更像刷子。

昂克领导并于近期发表在《自然·通讯》上的一项建模研究表明，中央运输通道可能有些部分是刷状的，而另一些则类似于凝聚物——一种无膜的、类似液体的区室，具有凝胶和刷子的特性。穆瑟说，甚至有可能通道密度较高的中心区域具有更像凝胶或凝聚物的性质，而外围则更像刷子。

霍尔茨说，只有能够完全看清核孔内部的新技术才能解决这场争论——而这些技术可能随时出现。

“人们一直在努力开发新的工具或新的策略，试图弄清楚发生了什么，”穆瑟表示同意。2025年，他和他的团队在《自然》杂志上发表了研究成果，使用一种名为Minflux的强大3D成像工具，以高分辨率追踪分子在人类细胞完整细胞核中穿过核孔复合体的过程。了解这种方法对霍尔茨来说是“一个彻底的改变游戏规则的事情”，他未参与该研究。

穆瑟的团队观察到分子只在运输通道的边缘附近移动。考虑到中央栓可能阻塞了中心，这也与劳特和林的研究相互补充。“但中心不被利用是说不通的，”穆瑟说。“我认为我们只是还没有找到合适的底物或开发出合适的工具来观察物质从中间通过。”

无论内部看起来是什么样子，很明显核孔复合体具有惊人的可塑性和鲁棒性——这也使其成为细胞的“阿喀琉斯之踵”，劳特说。它对细胞的健康至关重要，并且是其最重要的过程——蛋白质生产和基因调控——的核心。但正因为它有弹性且能承受损伤，它可能被疾病改变而不会完全关闭。

构成核孔的一些蛋白质“一次又一次地作为疾病的弱点出现，”劳特说，包括神经发育障碍、病毒性疾病和癌症。癌细胞和病毒都可能干扰复合体中的蛋白质，以使蛋白质制造机制对自身有利，或关闭免疫反应。

从这个意义上说，核孔复合体远不止是一个分子门。“它是信息整合的枢纽，”劳特说。“我想，如果细胞有思想，它就是这样看待它的核孔的。”

英文来源：

Disorder Drives One of Nature’s Most Complex Machines
Introduction
At the dawn of complex life, evolution created a container for DNA, its most treasured item. A few billion years later, 20th-century microscopists looked at this container — the nucleus — up close and saw that it was covered in tiny openings. At the time, they didn’t know what to make of these structures, but as microscopy improved, something grand came into focus: what we now call “nuclear pore complexes,” some of the largest and most marvelous molecular machines ever formed.
Every nuclear pore complex is constructed from hundreds of proteins, of around 30 different types. From the front, it looks like an eight-petaled flower; from the side, like a flying saucer. Its center opening spills over with spaghetti-like proteins tethered to the inner walls of the complex.
“It’s a thing of enormous beauty,” said Brian Chait, a chemical biologist at Rockefeller University. “It’s marvelous. It’s a wonder. … It’s phenomenal.”
This machine has a vital job: directing molecular traffic into and out of the nucleus. More than an open door, the protein complex recognizes different molecules as they approach — and lets only some through. “The nuclear pore complex is ultimately the gatekeeper for the nucleus,” said Roderick Lim, a biophysicist at the University of Basel in Switzerland. “Everything that has to get in and out of the nucleus has to go through these pores.”
Nearly every eukaryotic cell has a nucleus punctured with nuclear pore complexes, and the main components of the complex are incredibly conserved across species, from single-celled yeasts to multicellular humans. Evolution “came up with that thing one time and got stuck with it,” said André Hoelz, a structural cell biologist at the California Institute of Technology.
A single mammalian nucleus can contain thousands of them. Every second, each nuclear pore lets hundreds to thousands of molecules of all shapes and sizes pass through so that they can travel to their destinations to make proteins, regulate genes, and generally help the cell function. Some large molecules are carried through the channel by proteins, while small ones diffuse across on their own. And while some effortlessly glide through, to others it is an impenetrable barrier.
How this gate works with such selectivity is a mystery. Over decades, biologists have worked out what most of the static parts of the machine look like. But its center is restless, endlessly moving and morphing, which makes it difficult for even the best methods to visualize.
That’s gradually changing. In a study published in Nature Cell Biology at the end of 2025, high-resolution microscopy showed the central barrier in motion at millisecond resolution, revealing a flexible structure that constantly rearranges itself. The experimental imaging, backed by computational modeling, suggests that the function of the nuclear pore complex is guided by flexibility and movement.
This is more than an intellectual curiosity. A surge of recent research has linked neurodevelopmental disorders, viral disease, and cancers to problems with the complex. If biologists can discern how its cellular trafficking system works, they could develop methods to stop unwanted pathogens from getting through — and also try to guide therapeutic molecules into the cell nucleus, where the genome itself awaits.
“We are starting to approach a near-atomic picture of nuclear pores from various organisms,” said Mike Rout, a cell biologist at Rockefeller University who led the new work that offers insight into a molecular machine at the heart of eukaryotic life.
A Thing of Beauty
For many scientists who study the nuclear pore, it was an instant fascination: They were awed that this (relatively) massive biological machine could allow so many kinds of molecules, and so many of them, to move in and out of the nucleus efficiently, with little room for error.
“It is beautiful,” Hoelz said. “How do you generate an aircraft hangar that has a door where a 747 can go through,” but a small marble can’t fly out?
Somehow the gate itself must play bouncer for life’s important molecules. RNA molecules must get out of the nucleus to the cytoplasm to make proteins. Ribosomes, the structures that do the protein-making, are themselves made of molecules assembled in the nucleus and moved out through the pores. Meanwhile, molecules involved in regulating the genome must be ushered into the nucleus preferentially. As these processes unfold, the nuclear pore is also blocking things that don’t belong, such as harmful enzymes or misfolded RNAs.
Lori Chertoff/Rockefeller University
In the decades since the discovery of the nuclear pore complex, biologists have slowly gained a greater understanding of its structure using electron microscopy, tools of physics, and computer modeling. With the advent of cryo-electron microscopy, a powerful technique that images cells after flash-freezing them, they have been able to assess the static parts of the machine. These efforts have generated a near-atomic view of each individual protein that builds the eight petal-like radial units. But the technique hasn’t worked for the very center, called the transport channel, where most of the pore’s action happens.
“Whenever anyone uses some of these microscopes to peer inside nuclear pores, they just see this amorphous cloud inside,” Lim said. “It’s like a haze.”
The reason, which became apparent in the 1990s, is that the center of this giant machine is filled with proteins that have no obvious or specific structure. These proteins, called FG-nucleoporins, have tails that wiggle around like seaweed and that can’t be captured in static images. These tails are “the dark matter of the nuclear pore complex,” Hoelz said.
Most proteins fold into specific structures or shapes essential to the functions they perform in a cell. But intrinsically disordered proteins, a category that includes these nucleoporins, don’t have a single structure. They flail about, changing shape and binding to different molecules.
This means that in the center of the nuclear pore complex, “everything is mediated by disorder,” said Patrick Onck, a computational physicist at the University of Groningen in the Netherlands. “It’s not order that generates this function. It’s disorder.”
In the early 2000s, the field was awash with bickering about the organization and behavior of FG-nucleoporins in the transport channel and how they might traffic molecules into and out of the nucleus. Researchers agreed that most macromolecules can’t get through the channel without the help of cargo-carrying proteins called transport factors. Transport factors, which mingle with the nucleoporins in the channel, bind only to those molecules that include a specific short stretch of amino acids — a molecular tag that “says, in effect, ‘send me into the nucleus,’” Rout said. But researchers differed on how the channel itself might be organized, which would impact how molecules move through it. Some argued that nucleoporins snap onto one another, forming a gel-like mesh network. Others argued that the disordered proteins don’t interact with each other much, but rather constantly undulate like bristles on a brush.
The debate became contentious. “It used to be very hostile,” Hoelz recalled. “People are very passionate about what they’re doing. It’s not a personal animosity.”
“For a very long time, it was like, ‘Are you a gel person, or are you a brush person?’ You’re one or the other,” said Siegfried Musser, a cell biologist at Texas A&M University.
Biozentrum, University of Basel
In recent years, new collaborations and discussions, including at an annual conference where the principals gather to chat, have quieted the conflict. But the truth about the structure and functioning of the transport channel hadn’t been resolved. The researchers would need to get more creative to understand how the complex functions in its native environment.
“We wanted to simply go back to the nuclear pore complex and really ask the nuclear pore to tell us what it’s doing,” Rout said, “not for us to impose on it what it’s doing.”
Fast Tapper
How do you interrogate a molecular complex? Rout and Lim, who have both advocated for a more dynamic model of the nuclear pore, started with a simple idea: Poke it.
Rout has spent decades characterizing yeast pore complexes. Lim is an expert on high-speed atomic force microscopy, a technique that runs a very sharp probe over a surface, lightly and rapidly tapping it, to get a sense of how it moves.
A few years ago, in a dark basement laboratory, Lim’s graduate student Toshiya Kozai began unpacking plastic vials containing millions of yeast nuclear pore complexes. He toiled for days in the “dungeon of our department,” Lim recalled, working nonstop to get the samples into the high-speed atomic force microscope while they were fresh. “It’s a real labor of love.”
His efforts enabled the team to watch the transport channel change, millisecond by millisecond. “We could see very clear, super rapid motion,” Rout recalled. The resulting videos may look blurry to us macroscopic creatures, but they are some of the highest-definition looks at the behavior of the nanoscopic transport channel.
At the edges of the channel, near the walls, Rout and Lim’s team saw rapid fluctuations of molecules — those were the wiggly nucleoporins. At the center they saw a fuzzy blob, known as the central plug, that continuously moved around and repositioned itself within the transport channel. For a long time, biologists had suspected that a central plug might exist, but in previous microscopy images it wasn’t always visible.
“Seeing is believing,” said Hoelz, who was not involved in the study. To be able to show this “is a beautiful thing.”
Led by Chait and using mass spectrometry, the team discovered that the plug was made of transport proteins called karyopherins, or “kaps” for short, plus their molecular cargo. As kaps move through the nuclear pore, they latch onto the nucleoporins, tugging them toward the channel’s center. This creates a temporary, dynamic obstacle that slows other molecules or stops them from moving through. In that way, kaps not only help carry molecules across, but also push away anything that’s not supposed to be there, Rout said. When they added in more transport factors, they saw the plug grow bigger.
The heart of the nuclear pore complex is being constantly rearranged by kaps, creating an ever-changing environment. The results suggest that the pore’s organization and behavior are much more dynamic than a gel network, Rout said, and much closer to a brushlike environment. The findings support a model he previously proposed called the “virtual gate” in which the dynamics of the environment is critical for directing proteins away or through. He likened it to a crowded dance floor.
“If you know how to dance, you can simply enter the dance and swing from partner to partner, holding hands, just quickly exchanging going across,” he said. “If you don’t know how to dance, all you see is this turbulent melee, and you try to get in. No one’s taking hold of you to help you enter the dance, so you just get pushed away.”
To further test their observations, Rout and Lim created synthetic pores the same size as natural nuclear pore complexes. When they tethered nucleoporins inside and added transport factors, the synthetic pores behaved like the wild yeast nuclear pore complexes. They saw the central plug appear.
“What I find actually very striking is that they reproduce the result with a very simple model,” Musser said. “It’s a pretty stunning result.”
Door Not Closed
Hoelz is not totally convinced that this is a nail in the coffin for the gel model. The “answer is [probably] somewhere in the middle, which is very often the case in science,” he said. Researchers likely catch the central channel in different configurations because it’s changing all the time, he suggested, or perhaps the inner channels of some nuclear pores are more like a gel and others are more like a brush.
One recent modeling study led by Onck and published in Nature Communications suggested that the central transport channel could have some parts that are brushlike and others that are similar to condensates — membraneless, liquidlike compartments that have characteristics of gels and brushes. It could even be the case that the channel’s denser center has qualities more like a gel or condensate, Musser said, while the periphery is more brush-like.
Hoelz said that only new technologies that can fully see inside the pore will resolve the debate — and they could come any day now.
“People are constantly trying to develop new tools or new strategies to try to figure out what’s going on,” Musser agreed. In 2025, he and his team published results in Nature that used a powerful 3D imaging tool called Minflux to trace molecules in high resolution as they move through nuclear pore complexes in intact nuclei of human cells. Learning of this method was “a complete game changer for me,” said Hoelz, who was not involved.
Musser’s team observed molecules moving only near the edge of the transport channel. This also complements Rout and Lim’s study, given that the central plug might be blocking the center. “But it doesn’t make sense for the middle not to be used,” Musser said. “I think we just haven’t found the right substrate or developed the right tools to see stuff go through the middle.”
No matter what the inside looks like, it’s clear that the nuclear pore complex is incredibly malleable and robust — which also makes it the cell’s “Achilles’ heel,” Rout said. It is critical to a cell’s health, and central to its most important processes: protein production and gene regulation. But because it is resilient and can endure damage, it can be altered by disease without shutting down.
Some proteins that make up the nuclear pore “show up again and again and again as weak spots for disease,” Rout said, including neurodevelopmental disorders, viral diseases, and cancers. Both cancer cells and viruses likely interfere with proteins in the complex to swing the protein-making machinery in their favor or shut down an immune response.
In that sense, the nuclear pore complex is far more than a molecular gate. “It’s a nexus for integration of information,” Rout said. “And I think if the cell had thoughts, that would be how it thinks of its nuclear pores.”