© 1998 American Heart Association, Inc.
Editorial |
-Tropomyosin Knockouts
A Blow Against Transcriptional Chauvinism
Correspondence to J. Robbins, PhD, Division of Molecular Cardiovascular Biology, 3333 Burnet Ave, Cincinnati, OH 45229-3039. E-mail jeff.robbins@chmcc.org
Key Words: tropomyosin • transgenic • muscle • cardiomyopathy • gene
The pace at which the protein complement
of the heart is precisely remodeled by either gene targeting or
transgenesis in animal models continues to accelerate.1 A
logical focus of these approaches has been to establish
structure-function relationships of the proteins present in the
terminally differentiated cardiomyocyte. Rather
unexpectedly, these experiments have also highlighted the importance of
multiple control points, both at the transcriptional and
posttranscriptional levels, which are able to regulate the overall
stoichiometry of the cardiac thick and thin filament proteins. Several
recent articles in Circulation Research illustrate these
points for the thin filament protein, -tropomyosin
(-TM).2 3 4 In striated muscle, the thin filament
consists largely of actin, tropomyosin (TM), and the troponin complex
(troponins I, C, and T) and is responsible for mediating
Ca2+ control of contraction and relaxation. TM is a rigid
rod-shaped protein that binds along the length of the actin filament
and is intimately associated with troponin. It both stabilizes and
stiffens the filament.5 In the absence of Ca2+
binding to troponin C, TM blocks the myosin binding site of actin. TM
is a small polypeptide, 
284 amino acids, depending on the particular
isoform, and dimerizes to form a head-to-tail coiled-coil structure
that lies in the major groove of the actin filament. The placement of
the TM dimer is consistent with one of its important roles,
which is to help mediate cooperativity of Ca2+ activation
along the length of the myofilament.6 7
Like other sarcomeric proteins, TM exists as a set of isoforms; these
are generated
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 I. J. Benjamin and D. R. McMillan Stress (Heat Shock) Proteins : Molecular Chaperones in Cardiovascular Biology and Disease Circ. Res., July 27, 1998; 83(2): 117 - 132. [Abstract] [Full Text] [PDF]
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