Molecular architecture of myelin - the roles of intrinsically-disordered myelin basic proteins

大脑是人体中最复杂的器官，可以细分为灰质和白质。白质由髓鞘形成，富含形成膜的脂类。髓鞘是包裹在中枢神经系统(CNS)轴突(神经)周围的膜性螺旋，使它们能够有效地传递冲动。中枢神经系统髓鞘是由称为少突胶质细胞的细胞膜延伸形成的--一个少突胶质细胞可以包裹几种不同的神经纤维。髓鞘的形成是一个复杂的过程，分阶段发生。在每个阶段，必须严格控制基因表达，以产生适量的许多不同成分，然后需要将这些成分输送到细胞中的正确位置。即使在成熟的大脑中，髓鞘蛋白质和脂肪也会不断地周转和补充。当人们在电子显微镜下观察髓鞘时，人们看到的主要是致密的髓鞘，但也有较不致密的环状区域。更仔细的观察表明，髓鞘由不同的“微域”组成，可以通过使用洗涤剂的生化提取来“解剖”出来。这些不同类型的微域不仅在其组成蛋白质和脂类的组成上有所不同，而且在这些蛋白质在合成后如何被不同的酶修饰(最后一个过程被称为“翻译后修饰”)方面也不同。我们的研究旨在了解中枢神经系统髓鞘蛋白的修饰模式在发育过程中如何动态变化，以及在正常成人髓鞘中如何在空间上发生变化。我们使用各种生化、生物物理和细胞生物学工具来做到这一点，并为本科生和研究生提供学术和技术培训。

The brain is the most complex organ in the body and can be subdivided into gray and white matter. White matter is formed by myelin, and is highly enriched in lipids forming a membrane. The myelin sheath is a membranous spiral that wraps around the axons (nerves) of the central nervous system (CNS), and enables them to transmit impulses efficiently. The CNS myelin is formed by extensions of membranes of cells called oligodendrocytes - one oligodendrocyte can enwrap several different nerve fibers. The formation of myelin is a complex process that occurs in stages. At each stage, gene expression must be strictly controlled to produce the right amounts of many different components that then need to be delivered to the correct location in the cell. Even in the mature brain, there is constant turnover and replenishment of myelin proteins and lipids. When one looks at myelin in the electron microscope, one sees mainly compact myelin, but also less compact loop regions. An even closer look indicates that myelin consists of different "microdomains" that can be "dissected" out by biochemical extractions with detergents. These various types of microdomains differ both in composition of their constituent proteins and lipids, but also in how these proteins have been modified by different enzymes after synthesis (this last process is called "post-translational modification"). Our research aims to understand how the modification pattern of CNS myelin proteins varies dynamically during development, and spatially in normal adult myelin. We use a variety of biochemical, biophysical, and cell biological tools to do so, and provide scholarly and technical training for undergraduate and graduate students.