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

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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 sarcomere-associated 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.

Original languageEnglish
Pages (from-to)285-305
Number of pages21
JournalAdvances in Experimental Medicine and Biology
Publication statusPublished - 1984

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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