1. Introduction and Historical Perspective............................ 1 Peter Gunning Abstract................................................................................. 1 Introduction........................................................................... 1 Discovery and Context of Tropomyosin Research................ 1 Genes and their Expression (Chapters 2-4).......................... 2 Protein Structure (Chapters 5, 6)........................................... 3 Role in Muscle Function (Chapters 7-9)............................... 3 Tropomyosin in Human Disease (Chapters 10-13).............. 3 Tropomyosin Directed Regulation of the Cytoskeleton (Chapters 14-16)............... 4 Mechanisms of Tropomyosin Function (Chapters 17-21)........................................ 4 Section I. Genes and Their Expression 2. Structure and Evolution of Tropomyosin Genes............. 6 Bernadette Vrhovski, Nadine Thézé and Pierre Thiébaud Abstract.............................................................................. 6 Introduction........................................................................ 6 Structure of Tropomyosin Genes........................................ 7 Evolution of the Tropomyosin Genes................................. 18 Concluding Remarks.......................................................... 23 3. Tropomyosin Exons as Models for Alternative Splicing......................................................... 27 Clare Gooding and Christopher W.J. Smith Abstract............................................................................ 27 Introduction...................................................................... 27 Splicing Mechanism......................................................... 30 Analysis of Alternative SplicingMechanisms................. 30 ß-Tropomyosin—Tpm2................................................... 32 a-Tropomyosin Exons 2a and 2b..................................... 36 Other Tm Splicing Events................................................ 37 Concluding Remarks: Common Themes, General Insights and Future Directions............................................................................... 38 4. Tropomyosin Gene Expression in Vivo and in Vitro.......... 43 Galina Schevzov and Geraldine O’Neill Abstract.................................................................................. 43 Introduction............................................................................ 43 Temporal Alterations in Tm Isoform Expression during Development................... 44 A common Pattern of Tm expression During Cell Differentiation........................... 47 Functional Significance of Regulated Isoform Expression...................................... 48 Mechanisms Regulating Tm Expression................................. 49 Conclusions............................................................................ 53 References............................................................................. 53 Section II. Protein Structure 5. Tropomyosin: Function Follows Structure........................ 60 Sarah E. Hitchcock-DeGregori Abstract................................................................................. 60 Introduction........................................................................... 60 The Tropomyosin Coiled Coil.............................................. 60 The Tropomyosin Interface: Unstable Regions Interrupt Canonical Coiled Coil ........ 61 The Intermolecular Complex................................................. 64 Actin Binding Sites on
