Titin and Its associated proteins: the third myofilament system of the sarcomere

Abstract

This chapter describes titin, the third myofilament of the sarcomere, and outlines the early history that led to the discovery of titin. The chapter also discusses the functional genomics of titin, including an extensive discussion of differential splicing in the I-band region of the molecule. This region is elastic and the molecular mechanism of this elasticity and the way it can be modulated by differential splicing and posttranslational modifications is reviewed in the chapter. Ultrastructural studies with antibodies specific to titin's I-band region have demonstrated that titin's central I-band region behaves extensibly on myofibrillar stretch. The analysis of titin's primary structure revealed specific motif families within its I-band region that act as molecular springs: (1) tandem Ig segments, (2) the PEVK segment, and (3) the N2B-Us segment. The first two elements are found in both skeletal muscle and cardiac muscle titins, but the N2B-Us is cardiac specific. The chapter discusses the titin-binding proteins, including the possible roles of titin-based protein complexes in cell signaling.