Lai C, Watson J B, Bloom F E, Sutcliffe J G, Milner R J
Division of Preclinical Neuroscience and Endocrinology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Immunol Rev. 1987 Dec;100:129-51. doi: 10.1111/j.1600-065x.1987.tb00530.x.
We have reviewed the structure and properties of the neural protein 1B236/MAG. This molecule consists largely of five Ig-like domains separated from its carboxyl terminal tail by a single membrane-spanning region. Two forms of the protein differ in the length and sequence of the carboxyl terminus: these are encoded by alternatively spliced mRNAs that are differentially expressed during postnatal neural development. The Ig-like domains of 1B236/MAG are unusual in having structural similarities to Ig V domains but with short Cys-Cys distances characteristic of C domains. Several other Ig-like molecules exhibit this structural feature, including the cell adhesion molecule N-CAM, which is most closely related in sequence to 1B236/MAG. We have proposed 1B236/MAG as the prototype for this subgroup of the Ig family and offer a model for this type of Ig domain structure. 1B236/MAG probably acts as a cell adhesion molecule to mediate interactions between cells in a fashion similar to that proposed for N-CAM. In particular, 1B236/MAG may be involved in interactions between myelinating oligodendrocytes or Schwann cells and axons or between adjacent layers of myelin membrane during the process of myelin compaction. It is most likely that the homophilic or heterophilic interactions of 1B236/MAG occur through binding to the Ig-like domains. The structure of 1B236/MAG is therefore quite consistent with its proposed function and may serve as the model for this class of cell-cell interaction molecules. One would predict, for example, that the neuron-glia cell adhesion molecule Ng-CAM, also known as NILE or L1 (Bock et al. 1985, Friedlander et al. 1985), which mediates interactions between neurons and glial cells, would have a very similar structure to those of N-CAM and 1B236/MAG. In addition, the carboxyl terminal tails of the 1B236/MAG proteins may also be involved in interactions with cytoskeletal components, during membrane vesicle transport through the glial cytoplasm during myelination or through neuronal axoplasm or cytoplasm. The availability of full-length cDNA clones of 1B236/MAG mRNAs with the ability to express these products in vitro will enable the structure and interactions of 1B236/MAG to be tested in detail.
我们已对神经蛋白1B236/MAG的结构和特性进行了综述。该分子主要由五个免疫球蛋白(Ig)样结构域组成,通过单个跨膜区域与其羧基末端尾巴分隔开。该蛋白的两种形式在羧基末端的长度和序列上有所不同:它们由选择性剪接的mRNA编码,这些mRNA在出生后神经发育过程中差异表达。1B236/MAG的Ig样结构域不同寻常,其与Ig V结构域具有结构相似性,但具有C结构域特有的短半胱氨酸-半胱氨酸距离。其他几种Ig样分子也表现出这种结构特征,包括细胞粘附分子N-CAM,其在序列上与1B236/MAG关系最为密切。我们已将1B236/MAG提议为Ig家族这一亚组的原型,并为这种类型的Ig结构域结构提供了一个模型。1B236/MAG可能作为一种细胞粘附分子,以类似于N-CAM所提出的方式介导细胞间的相互作用。特别是,1B236/MAG可能参与髓鞘形成过程中髓鞘少突胶质细胞或施万细胞与轴突之间或髓鞘膜相邻层之间的相互作用。1B236/MAG的同嗜性或异嗜性相互作用很可能是通过与Ig样结构域结合而发生的。因此,1B236/MAG的结构与其所提议的功能相当一致,并且可能作为这类细胞-细胞相互作用分子的模型。例如,可以预测,介导神经元与胶质细胞之间相互作用的神经元-胶质细胞粘附分子Ng-CAM,也称为NILE或L1(博克等人,1985年;弗里德兰德等人,1985年),其结构与N-CAM和1B236/MAG的结构非常相似。此外,1B236/MAG蛋白的羧基末端尾巴在髓鞘形成过程中通过胶质细胞质或通过神经元轴质或细胞质进行膜泡运输期间,也可能参与与细胞骨架成分的相互作用。能够在体外表达这些产物的1B236/MAG mRNA全长cDNA克隆的可得性,将使我们能够详细测试1B236/MAG的结构和相互作用。