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

大脑是身体中最复杂的器官，可分为灰质和白色物质。白色物质由髓磷脂形成，并且高度富集形成膜的脂质。髓鞘是一种膜螺旋，包裹在中枢神经系统（CNS）的轴突（神经）周围，使它们能够有效地传递冲动。中枢神经系统髓鞘是由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个不同的神经纤维。髓鞘的形成是一个分阶段发生的复杂过程。在每个阶段，基因表达必须严格控制，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，髓鞘蛋白和脂质也会不断更新和补充。当我们在电子显微镜下观察髓鞘时，我们看到的主要是致密的髓鞘，但也有不那么致密的环区。更仔细的观察表明，髓磷脂由不同的“微区”组成，可以通过用去污剂进行生化提取而“解剖”出来。这些不同类型的微结构域不仅在其组成蛋白质和脂质的组成上不同，而且在这些蛋白质在合成后如何被不同的酶修饰上也不同（最后一个过程被称为“翻译后修饰”）。我们的研究旨在了解CNS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的空间变化。我们使用各种生物化学，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.