Mencel Marshal L, Bittner George D
Institute of Cell and Molecular Biology, University of Texas at Austin, Austin, TX, United States.
Department of Neuroscience, University of Texas at Austin, Austin, TX, United States.
Front Physiol. 2023 Mar 15;14:1114779. doi: 10.3389/fphys.2023.1114779. eCollection 2023.
Neuroscientists and Cell Biologists have known for many decades that eukaryotic cells, including neurons, are surrounded by a plasmalemma/axolemma consisting of a phospholipid bilayer that regulates trans-membrane diffusion of ions (including calcium) and other substances. Cells often incur plasmalemmal damage traumatic injury and various diseases. If the damaged plasmalemma is not rapidly repaired within minutes, activation of apoptotic pathways by calcium influx often results in cell death. We review publications reporting what is less-well known (and not yet covered in neuroscience or cell biology textbooks): that calcium influx at the lesion sites ranging from small nm-sized holes to complete axonal transection activates parallel biochemical pathways that induce vesicles/membrane-bound structures to migrate and interact to restore original barrier properties and eventual reestablishment of the plasmalemma. We assess the reliability of, and problems with, various measures (e.g, membrane voltage, input resistance, current flow, tracer dyes, confocal microscopy, transmission and scanning electron microscopy) used individually and in combination to assess plasmalemmal sealing in various cell types (e.g., invertebrate giant axons, oocytes, hippocampal and other mammalian neurons). We identify controversies such as plug patch hypotheses that attempt to account for currently available data on the subcellular mechanisms of plasmalemmal repair/sealing. We describe current research gaps and potential future developments, such as much more extensive correlations of biochemical/biophysical measures with sub-cellular micromorphology. We compare and contrast naturally occurring sealing with recently-discovered artificially-induced plasmalemmal sealing by polyethylene glycol (PEG) that bypasses all natural pathways for membrane repair. We assess other recent developments such as adaptive membrane responses in neighboring cells following injury to an adjacent cell. Finally, we speculate how a better understanding of the mechanisms involved in natural and artificial plasmalemmal sealing is needed to develop better clinical treatments for muscular dystrophies, stroke and other ischemic conditions, and various cancers.
几十年来，神经科学家和细胞生物学家都知道，包括神经元在内的真核细胞被一层质膜/轴突膜所包围，该膜由磷脂双层组成，可调节离子（包括钙）和其他物质的跨膜扩散。细胞在遭受创伤性损伤和各种疾病时常常会发生质膜损伤。如果受损的质膜在几分钟内没有迅速修复，钙内流激活凋亡途径通常会导致细胞死亡。我们回顾了一些出版物，这些出版物报道了鲜为人知的内容（神经科学或细胞生物学教科书尚未涵盖）：从纳米级的小孔到完全的轴突横断，损伤部位的钙内流会激活平行的生化途径，诱导囊泡/膜结合结构迁移并相互作用，以恢复原来的屏障特性并最终重新建立质膜。我们评估了单独或组合使用的各种测量方法（例如膜电压、输入电阻、电流、示踪染料、共聚焦显微镜、透射和扫描电子显微镜）用于评估各种细胞类型（例如无脊椎动物巨型轴突、卵母细胞、海马和其他哺乳动物神经元）质膜封闭的可靠性和存在的问题。我们确定了一些争议，例如试图解释目前有关质膜修复/封闭亚细胞机制现有数据的堵塞-补丁假说。我们描述了当前的研究差距和潜在的未来发展，例如生化/生物物理测量与亚细胞微观形态的更广泛关联。我们比较并对比了自然发生的封闭与最近发现的由聚乙二醇（PEG）人工诱导的质膜封闭，后者绕过了所有天然的膜修复途径。我们评估了其他最近的发展，例如相邻细胞受伤后邻近细胞中的适应性膜反应。最后，我们推测，为了开发针对肌肉萎缩症、中风和其他缺血性疾病以及各种癌症的更好临床治疗方法，需要更好地理解自然和人工质膜封闭所涉及的机制。
