LENS PROTEIN ALPHA-CRYSTALLIN B CHAIN

α-晶体蛋白是脊椎动物晶状体的主要成分， 由A链和B链两个亚基组成。这两个 蛋白质有许多相同的氨基酸序列，但表现出不同的模式 组织表达。虽然A链似乎是特定于镜头的，但最近 研究表明，B链存在于多种组织中，包括 心脏和骨骼肌、脑、肾、周围神经和肺。 事实上，心肌中的mRNA和蛋白质水平接近于晶状体中的水平。 在中枢神经系统中，B链存在于胶质细胞中，包括星形胶质细胞和 少突胶质细胞。虽然正常中枢神经系统中的水平很低，但B链 在病理情况下表达增加，特别是在 包括缺氧和血脑屏障的破坏。最多的 B链的惊人和奇怪的表达发生在 患有亚历山大病的儿童，这是一种退行性疾病，通常 会影响幼儿，并在几年内导致死亡。在亚历山大的 疾病，星形胶质细胞在整个中枢神经系统积累大量的B 链，沉积在中间丝束上。这些 堆积一直被称为罗森塔尔纤维，但直到最近， 对它们的组成和来源一无所知。 结构性质、信使核糖核酸序列和基因组 对A链和B链的结构进行了广泛的研究 研究人员对晶状体蛋白质感兴趣。在其他生物中发现B链 组织开启了对生物学的大范围探索 这一蛋白质的特性和调控一直难以 接近镜头。我们建议研究B链的几个方面 镜头外的表情。具体来说，以下问题将 被问到：1.B链的亚细胞定位是什么？它是 一种中间纤维相关蛋白？它是一种膜相关的 蛋白质？2.8链是一种受病理调控的“应激”蛋白质吗？ 刺激，如果是，是什么类型的刺激？3.罗森塔尔纤维如何 是在星形胶质细胞中形成的？这些研究应该会为 α-晶体蛋白B链的性质并阐明两种晶状体 上皮细胞和非晶状体细胞使用这种蛋白质。

Alpha-crystallin, a major component of the vertebrate lens, is composed of two subunits, the A Chain and the B Chain. These two proteins share many amino acid sequences, but show different patterns of tissue expression. While the A chain appears to be lens-specific, recent studies have demonstrated B chain in a variety of tissues, including cardiac and skeletal muscle, brain, kidney, peripheral nerve, and lung. Indeed, mRNA and protein levels in cardiac muscle approach those in lens. In the CNS, the B chain is found in glial cells, both astrocytes and oligodendrocytes. Although levels in normal CNS are low, B chain expression is increased in pathological circumstances, particularly those involving hypoxia and breakdown of the blood brain barrier. The most striking and bizarre expression of the B chain occurs in the brains of children with Alexander's disease, a degenerative disorder that typically affects young children and leads to death in a few years. In Alexander's disease, astrocytes throughout the CNS accumulate massive quantities of B chain, deposited on bundles of intermediate filaments. These accumulations have been called Rosenthal fibers, but until recently, nothing was known of their composition or origin. The structural properties, mRNA sequence, and genomic structures of both A and B chain have been studied extensively by investigators interested in lens proteins. Finding the B chain in other tissues opens up a large range of explorations into the biological features and regulation of this protein that have been difficult to approach in the lens. We propose to study several aspects of B chain expression outside the lens. Specifically, the following questions will be asked: 1. What is the subcellular localization of the B chain? It is an intermediate filament-associated protein? Is it a membrane-associated protein? 2. Is the 8 chain a "stress" protein, regulated by pathological stimuli, and if so, what kinds of stimuli? 3. How might Rosenthal fibers be formed in astrocytes? These studies should shed new light on the properties of the alpha-crystallin B chain and illuminate how both lens epithelial cells and non-lens cells use this protein.