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Biomedical Sciences | Tropomyosin

Tropomyosin

Gunning, Peter (Ed.)

2008

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A recent review of one of my grant applications commented on the ‘rediscovery of tropomyosin’. I was tempted to write back in my rebuttal to the reviewer that I didn’t realise it had been lost. Uncharacteristic maturity prevailed and I resisted the temptation, but I was struck by the underlying observation that research on the str- ture and function of tropomyosin has been somewhat invisible, particularly in terms of the cytoskeleton isoforms. So, how can it be that one of the two major components of the actin filament has been so thoroughly overlooked? I suspect that the answer is disappointingly pedestrian. Whereas the biochemistry of the 1980s revealed the potential of tropomyosin isoforms to diversify the function of actin filaments, the subsequent disenchantment with isoform biology in general in the 1990s inhibited growth of this field. With the development of more sophisticated experimental - proaches we are now seeing a growing realisation of the importance of tropomyosin in regulating actin filaments beyond its pivotal role in muscle contraction. The opportunity to edit this book came at a time when we had written several reviews on different aspects of tropomyosin function and I had just finished the background reading for a comprehensive review of tropomyosin biology. I realised that the field was simply beyond the capacity of any one person to do the field j- tice.

Content Level » Research

Keywords » cancer - cell differentiation - dynamics - gene expression - protein - protein structure - proteins - regulation

Related subjects » Biomedical Sciences

Table of contents 

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

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