Cytoskeletal matrix in striated muscle: the role of titin, nebulin and intermediate filaments.

Cytoskeletal matrix in striated muscle: the role of titin, nebulin and intermediate filaments.
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横纹肌中的细胞骨架基质:肌联蛋白、星云蛋白和中间丝的作用。

DOI:
10.1007/978-1-4684-4703-3_25
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发表时间:
1984
影响因子:
--
通讯作者:
Wang,K
Wang,K
中科院分区:
医学4区
文献类型:
--
作者:
Wang,K

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在本章中,首先我将简要描述两种极大的肌原纤维蛋白titin和nebulin的分子特性,并讨论它们在肌节中的分布和组织。尽管这些新蛋白质是大量横纹肌的主要肌纤维成分,但直到最近才引起肌肉生化学家的注意。正如我将在下面指出的那样,对这些蛋白质的生物化学研究出乎意料地具有挑战性:许多标准技术在能够处理如此巨大的蛋白质之前必须进行修改。此外,我们对这些蛋白质的结构研究遇到了一个不同性质的挑战:如何根据目前公认的两丝肌节模型来解释它们在肌节中的分布,因为这些蛋白质似乎并不是粗细丝相关的调节或锚定蛋白。这些研究使我们重新审视横纹肌肌节内是否存在连续的纵向细丝的问题。我将尝试整合我们的结果,以及现有的文献数据,在一个假设的肌节模型框架内,该模型包含由titin和nebulin组成的弹性丝状基质作为额外的肌节成分。最后,我将非常简要地提到我们最近的发现,一个广泛的三维网络的中间(10纳米)细丝,不同于titin和nebulin,与成人横纹肌肌节密切相关。我相信,在成人横纹肌纤维中存在两组与肌肉相关的细胞骨架细丝的认识可能是解决肌肉力学中一些未解决问题的重要一步,例如在本次会议上讨论的那些问题
In this chapter, first I will briefly describe the molecular properties of titin and nebulin — two extremely large, myofibrillar proteins -- and discuss their distribution and organization in the sarcomere. Although these novel proteins are major myofibrillar components of a wide range of striated muscles, they have escaped the attention of muscle biochemists until very recently. As I shall point out below, biochemical studies of these proteins have been unexpectedly challenging: many standard techniques had to be modified before they became capable of handling such giant proteins. In addition, our structural studies of these proteins have encountered a challange of a different nature: how to explain their distribution in the sarcomere according to the currently accepted two filament sarcomere model, because these proteins do not appear to be thick or thin filament-associated regulatory or anchoring proteins. These studies have led us to reexamine the question of whether continuous, longitudinal filaments exist within the sarcomere of striated muscle. I will attempt to integrate our results, as well as available literature data, within the framework of a hypothetical sarcomere model which incorporates an elastic filamentous matrix consisting of titin and nebulin as additional sarcomere constituents. Finally, I will very briefly mention our recent findings that an extensive three dimensional network of intermediate (10 nm) filaments, distinct from titin and nebulin, is intimately associated with the sarcomere of adult striated muscle.I believe that the recognition of the existence of two sets of sarcomereassociated cytoskeletal filaments within adult striated muscle fibers may be a significant step toward resolving some of the unsettled questions in muscle mechanics such as those that have been discussed in this meeting