2',3'‐Cyclic Nucleotide 3'‐Phosphodiesterase Has Characteristics of Cytoskeletal Proteins A Hypothesis for Its Function a
2',3'‐Cyclic Nucleotide 3'‐Phosphodiesterase Has Characteristics of Cytoskeletal Proteins A Hypothesis for Its Function a
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2,3-环状核苷酸 3-磷酸二酯酶具有细胞骨架蛋白的特征及其功能的假设
DOI：
10.1111/j.1749-6632.1990.tb42380.x
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发表时间：
1990
影响因子：
5.2
通讯作者：
L. Bernier
中科院分区：
文献类型：
--
作者：
P. E. Braun;L. Bambrick;A. Edwards;L. Bernier
最早出现的、在中枢神经系统中仅由髓鞘形成细胞表达的髓鞘形成相关多肽是2',3'-环核苷酸、3'-磷酸二酯酶(CNP)。 （有关综述，请参阅 Vogel 和 Thompson。'）这种蛋白质的 mRNA 在产前首次出现，并且早在髓鞘形成明显之前，该蛋白质本身就可以在少突胶质细胞中通过免疫细胞化学观察到，甚至在小鼠脑室下区域的假定少突胶质细胞祖细胞中也是如此。*事实上，我们和其他人3都没有在致密髓磷脂中观察到 CNP，但发现它集中在轴突和节旁环中的结构向我们表明，CNP 不太可能像主要结构蛋白（即蛋白脂质蛋白和髓磷脂碱性蛋白）那样对髓鞘的结构有贡献。 ~ CNP 然而与髓磷脂膜共分离，但这些可以通过密度梯度离心进行细分，随后在较致密的膜中出现 CNP（可能是源自旁节环的单层元素），这有助于常规分离的包含髓磷脂部分的膜谱（由 Danks 和 matt hie 审查^。^ 尽管大部分 CNP 酶活性与 CNS 髓磷脂共分离，但显着部分也与非髓磷脂膜部分相关。 6 这些观察结果与 CNP 与致密髓磷脂的富含脂质层有关的早期广泛观点不相容，多项研究 a 表明，CNP 分配到非离子去污剂中与细胞骨架或膜骨骼蛋白的分配行为相似，与观察到的内在膜蛋白的行为非常不同。 Sprinkle 和 HancockIo 确定 CNP 具有被认为参与 GTP 结合的三个结构域中的两个，即 GXXXXGKWT 和 DXXGIA。另一个结构域 YFGKRPPG 也存在于 CNP 中，所有这些结构域均与负责 CNP 磷酸二酯酶活性的假定催化结构域无关。此外，我们发现 C 末端结构域 CXXX 与某些结构域相同。 nonrus G 蛋白以及 ras 相关蛋白的 GTP 结合家族。
The earliest appearing, myelinogenesis-associated polypeptide expressed in the CNS exclusively by myelinating cells is 2',3 '-cyclic nucleotide, 3'-phosphodiesterase (CNP). (For a review see Vogel and Thompson.') The mRNA for this protein first appears prenatally, and the protein itself can be visualized immunocytochemically in oligodendrocytes long before myelination is evident, even in putative oligodendrocyte progenitors in the subventricular region of mouse brain.* The fact that neither we nor others3 observe CNP in compact myelin, but find it concentrated in the cytoplasm of noncompacted oligodendroglial ensheathments of axons and in the paranodal loops suggests to us that CNP does not likely contribute to the architecture of the myelin sheath as do the major structural proteins, namely, proteolipid protein and myelin basic p r ~ t e i n . ~ CNP nevertheless coisolates with myelin membranes, but these can be subfractionated by density gradient centrifugation with the subsequent appearance of CNP in the denser membranes (presumably unilamellar elements originating from the paranodal loops) that contribute to the spectrum of membranes comprising the myelin fraction as routinely isolated (reviewed by Danks and matt hie^.^ Although the bulk of CNP enzymatic activity coisolates with CNS myelin, a significant fraction is also associated with nonmyelin membrane fractions.6 The incompatibility of these observations with the earlier widespread view that CNP is affiliated with the lipidrich lamellae of compact myelin is further exemplified by the behavior of CNP towards extraction. Several studiesa show that the partitioning of CNP into nonionic detergents is similar to the partitioning behavior of cytoskeletal or membranoskeletal proteins and is very different from the observed behavior of intrinsic membrane proteins. Recently, we9 and Sprinkle and HancockIo determined that CNP possesses two of the three domains believed to participate in GTP binding. These are GXXXXGKWT and DXXGIA. Another domain, YFGKRPPG, known in other proteins for its adenine recognition capacity, is also present in CNP. All of these are apparently unrelated to the putative catalytic domain responsible for the phosphodiesterase activity of CNP. In addition, we found that the C-terminal domain, CXXX, is identical to that of some of the nonrus G proteins as well as the GTP-binding family of ras proteins. In ras-related