A new look at thin filament regulation in vertebrate skeletal muscle.
It is 30 years since Ebashi and colleagues showed that Ca2+ ions directly affect regulation of the myosin-actin interaction in muscle through the action of tropomyosin and troponin on muscle thin filaments. It is more than 20 years since the idea was put forward that tropomyosin might act, at least in part, by changing its position on actin, thus uncovering or modifying the myosin binding site on actin when troponin molecules take up Ca2+. Since that time, a great deal of evidence for and against this steric blocking mechanism has been published: a structure for actin filaments at close to atomic resolution has been proposed, and the whole regulation story has become both more complicated and more subtle. Here we review structural and biochemical aspects of regulation in vertebrate skeletal muscle. We show that some basic ideas of the steric blocking mechanism remain valid. We also show that additional factors, such as troponin movements and structural changes within the actin monomers themselves, may be crucial. A number of the resulting regulation scenarios need to be distinguished.
Squire
J M
JM
Biophysics Section, Blackett Laboratory, Imperial College, London, UK.
Morris
E P
EP
D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008854:Microscopy, Electron; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D014335:Tropomyosin / Q000737:chemistry* / Q000378:metabolism; D014336:Troponin / Q000737:chemistry* / Q000378:metabolism; D019209:Troponin C / Q000737:chemistry; D019210:Troponin I / Q000737:chemistry; D020107:Troponin T; D014961:X-Ray Diffraction
D000199:Actins; D014335:Tropomyosin; D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D020107:Troponin T; D002118:Calcium