一项新的研究显示了细胞膜是如何弯曲形成“嘴”的，这些“嘴”允许细胞吞噬它们周围的东西。
“就像我们的饮食习惯基本上塑造了我们身体的任何东西一样，细胞'吃’的方式也关系到细胞的健康，”俄亥俄州立大学(Ohio State University)物理学副教授、该研究的主要作者科默特·库尔(Comert Kural)说。“直到现在，科学家们才明白这是如何发生的。”
这项上个月发表在《发育细胞》(Developmental Cell)杂志上的研究发现，细胞的胞间机制组装成高度弯曲的篮状结构，最终生长成一个封闭的笼子。科学家们此前认为，这种结构开始于平面晶格。
库尔说，膜曲率很重要:它控制着携带物质进出细胞的囊袋的形成。
囊袋捕获细胞周围的物质，在细胞外物质周围形成，然后变成小泡——红细胞大小的百万分之一的小泡。囊泡携带着细胞健康的重要物质，例如蛋白质进入细胞。但它们也会被感染细胞的病原体劫持。
但是，这些口袋是如何从之前被认为是扁平的薄膜中形成的，这个问题困扰了研究人员近40年。
“这是细胞研究中的一个争议，”库尔说。“我们能够使用超分辨率荧光成像来实际观察这些口袋在活细胞内的形成，所以我们可以回答这些口袋是如何形成的问题。
“简单地说，与之前的研究相比，我们对细胞进行了高分辨率的拍摄，而不是拍快照，”库尔说。“我们的实验表明，蛋白质支架一旦被招募到囊泡形成的位置，就会开始变形下层膜。”
库尔说，这与之前的假设形成鲜明对比，之前的假设认为，细胞的蛋白质支架必须经过一次能量密集型重组，才能使细胞膜弯曲。
细胞消耗和排出囊泡的方式对生物体起着关键作用。这一过程有助于清除血液中的有害胆固醇;它也传送神经信号。这一过程在几种疾病中会被破坏，包括癌症和阿尔茨海默氏症。
Kural说:“了解膜结合的囊泡的起源和动力学是很重要的——它们可以被用来运送药物用于医学目的，但同时也会被病原体(如病毒)劫持，进入并感染细胞。”“我们的研究结果很重要，不仅对我们理解生命的基本原理，而且对开发更好的治疗策略也很重要。”
俄亥俄州立大学药学院助理教授Emanuele Cocucci与来自加州大学伯克利分校、加州大学河滨分校、爱荷华州立大学、普渡大学和中国科学院的研究人员共同撰写了这项研究。
More information: Nathan M. Willy et al, De novo endocytic clathrin coats develop curvature at early stages of their formation, Developmental Cell (2021). DOI: 10.1016/j.devcel.2021.10.019
Highlight:
Endocytic clathrin coats develop curvature starting from early stages of their formation
·Formation of clathrin pits does not depend on a late-stage flat-to-curved transition
·Membrane tension does not alter the mechanism of curvature generation by clathrin pits
·CALM adaptors form distinct clusters beneath the clathrin plaques
Summary
Sculpting a flat patch of membrane into an endocytic vesicle requires curvature generation on the cell surface, which is the primary function of the endocytosis machinery. Using super-resolved live cell fluorescence imaging, we demonstrate that curvature generation by individual clathrin-coated pits can be detected in real time within cultured cells and tissues of developing organisms. Our analyses demonstrate that the footprint of clathrin coats increases monotonically during the formation of pits at different levels of plasma membrane tension. These findings are only compatible with models that predict curvature generation at the early stages of endocytic clathrin pit formation. We also found that CALM adaptors associated with clathrin plaques form clusters, whereas AP2 distribution is more homogenous. Considering the curvature sensing and driving roles of CALM, we propose that CALM clusters may increase the strain on clathrin lattices locally, eventually giving rise to rupture and subsequent pit completion at the edges of plaques.
A new study shows how cell membranes curve to create the "mouths" that allow the cells to consume things that surround them.
"Just like our eating habits basically shape anything in our body, the way cells 'eat' matters for the health of the cells," said Comert Kural, associate professor of physics at The Ohio State University and lead author of the study. "And scientists did not, until now, understand the mechanics of how that happened."
The study, published last month in the journal Developmental Cell, found that the intercellular machinery of a cell assembles into a highly curved basket-like structure that eventually grows into a closed cage. Scientists had previously believed that structure began as a flat lattice.
Membrane curvature is important, Kural said: It controls the formation of the pockets that carry substances into and out of a cell.
The pockets capture substances around the cell, forming around the extracellular substances, before turning into vesicles—small sacs one-one millionth the size of a red blood cell. Vesicles carry important things for a cell's health—proteins, for example—into the cell. But they can also be hijacked by pathogens that can infect cells.
But the question of how those pockets formed from membranes that were previously believed to be flat had stymied researchers for nearly 40 years.
"It was a controversy in cellular studies," Kural said. "And we were able to use super-resolution fluorescence imaging to actually watch these pockets form within live cells, and so we could answer that question of how they are created.
"Simply put, in contrast to the previous studies, we made high-resolution movies of cells instead of taking snapshots," Kural said. "Our experiments revealed that protein scaffolds start deforming the underlying membrane as soon as they are recruited to the sites of vesicle formation."
That contrasts with previous hypotheses that the protein scaffolds of a cell had to go through an energy-intensive reorganization in order for the membrane to curve, Kural said.
The way cells consume and expel vesicles plays a key role for living organisms. The process helps clear bad cholesterol from blood; it also transmits neural signals. The process is known to break down in several diseases, including cancer and Alzheimer's disease.
"Understanding the origin and dynamics of membrane-bound vesicles is important—they can be utilized for delivering drugs for medicinal purposes, but at the same time, hijacked by pathogens such as viruses to enter and infect cells," Kural said. "Our results matter, not only for our understanding of the fundamentals of life, but also for developing better therapeutic strategies."
Emanuele Cocucci, an assistant professor in Ohio State's College of Pharmacy, co-authored this study, along with researchers from UC Berkeley, UC Riverside, Iowa State University, Purdue University and the Chinese Academy of Sciences.
文章来源网络整理；如有侵权请及时联系PaperRSS小编删除，转载请注明来源。
温馨提示：
为方便PaperRSS粉丝们科研、就业等话题交流。我们根据10多个专业方向（植物、医学、药学、人工智能、化学、物理、财经管理、体育等），特建立了30个国内外博士交流群。群成员来源欧美、日韩、新加坡、清华北大、中科院等全球名校。
联系客服
