Obscurins: Goliaths and Davids take over non-muscle tissues.
Obscurins: Goliaths and Davids take over non-muscle tissues.
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DOI：
10.1371/journal.pone.0088162
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kontrogianni-Konstantopoulos A
中科院分区：
文献类型：
--
作者：
Ackermann MA;Shriver M;Perry NA;Hu LY;Kontrogianni-Konstantopoulos A
Obscurins包括最初在横纹肌中鉴定的蛋白质家族，在那里它们在肌原纤维发生、细胞骨架组织和Ca 2+稳态中起重要作用。它们由单个OBSCN基因编码，并且由串联粘附结构域和信号基序组成。迄今为止，已经详细描述了两种巨大的obscurin亚型，它们仅在极端的COOH-末端不同;而obscurin-A（约720 kDa）含有一个非模块化的COOH-末端，其含有接头蛋白锚蛋白的结合位点，obscurin-B（约870 kDa）含有两个COOH-末端丝氨酸-苏氨酸激酶结构域，前面是粘附基序。除了两个已知的巨大的obscurin，转录本数据库的彻底搜索表明，复杂的选择性剪接的obscurin转录本的结果在产生额外的巨大的以及小的异构体与分子量范围在1050 -970 kDa之间。这些新的异构体与表征的异构体共享共同的结构域，但也包含独特的区域。使用一组高度特异性的抗体，针对跨越整个长度的巨大obscurins的表位，我们采用蛋白质印迹和免疫组织化学进行系统和全面的表征obscurins在肌肉和非肌肉组织中的表达谱。我们的研究首次证明，obscurin不仅限于横纹肌，但在几个组织和器官，包括脑，皮肤，肾脏，肝脏，脾脏和肺中大量表达。虽然一些obscurin同种型普遍表达，但其他同种型优先存在于特定组织和器官中。此外，暗蛋白存在于选择的结构和细胞类型中，其中它们呈现核、胞质和膜分布。考虑到一些obscurin的普遍表达，沿着其他obscurin的优先表达，很明显obscurin可能分别在调节和维持全身各种组织和器官中的细胞稳态中发挥共同和独特的作用。
Obscurins comprise a family of proteins originally identified in striated muscles, where they play essential roles in myofibrillogenesis, cytoskeletal organization, and Ca2+ homeostasis. They are encoded by the single OBSCN gene, and are composed of tandem adhesion domains and signaling motifs. To date, two giant obscurin isoforms have been described in detail that differ only at the extreme COOH-terminus; while obscurin-A (∼720 kDa) contains a non-modular COOH-terminus that harbors binding sites for the adaptor proteins ankyrins, obscurin-B (∼870 kDa) contains two COOH-terminal serine-threonine kinase domains preceded by adhesion motifs. Besides the two known giant obscurins, a thorough search of transcript databases suggests that complex alternative splicing of the obscurin transcript results in the generation of additional giant as well as small isoforms with molecular masses ranging between ∼50–970 kDa. These novel isoforms share common domains with the characterized isoforms, but also contain unique regions. Using a panel of highly specific antibodies directed against epitopes spanning the entire length of giant obscurins, we employed western blotting and immunohistochemistry to perform a systematic and comprehensive characterization of the expression profile of obscurins in muscle and non-muscle tissues. Our studies demonstrate for the first time that obscurins are not restricted to striated muscles, but are abundantly expressed in several tissues and organs including brain, skin, kidney, liver, spleen, and lung. While some obscurin isoforms are ubiquitously expressed, others are preferentially present in specific tissues and organs. Moreover, obscurins are present in select structures and cell types where they assume nuclear, cytosolic, and membrane distributions. Given the ubiquitous expression of some obscurins, along with the preferential expression of others, it becomes apparent that obscurins may play common and unique roles, respectively, in the regulation and maintenance of cell homeostasis in various tissues and organs throughout the body.
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