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First discovered by Bailey (Bailey, 1948), the tropomyosins are a group of proteins that bind to the sides of actin filaments and (together with troponins) regulate the interaction of the filaments with myosin in response to Ca2+.  They are parallel, a-helical, coiled coil dimers.  Vertebrates typically express in the region of 20 different tropomyosins from alternative spicing from about four tropomyosin genes (Perry, 2001 ).  Tropomyosins exist as both homo-dimers and hetero-dimers held together by a series of salt bridges and hydrophobic interactions. They may also interact through their N and C termini in solution (especially in low ionic strength buffers) and this can be monitored by viscosity. There are two major groups of tropomyosin the high and low molecular weight tropomyosins.  The former type exist primarily in muscle tissues (cardiac, smooth and skeletal) whereas non-muscle tissues express both high and low mol.wt. tropomyosins. 


Actin-Binding Properties.

Tropomyosins bind cooperatively to actin filaments (Wegner, 1979; Yang et al, 1979; Zot & Potter, 1987) probably because there is end-to-end binding of the tropomyosin molecules but possibly also because tropomyosin restricts the movement of the filament causing the filament repeat distance to be made more regular (Stokes & DeRosier et al, 1987). The binding of tropomyosin to actin is strongly Mg2+ dependent (Wegner, 1979).  High mol.wt. tropomyosins are most often 284 amino-acids and bind seven actin monomers, the low mol.wt. tropomyosins consist of about 245-250 amino-acids and span six actins.  This means that for every 14 actins in a filament there are two high mol.wt tropomyosins. 
The carboxy-terminal region of tropomyosin is important for strong actin-binding.  Unacetlyated striated muscle tropomyosin has a very low affinity for actin filaments (
Hitchcock-DeGregori & Heald, 1987; Cho et al, 1990) and does not associate with other tropomyosin dimers in the usual head to tail manner. Unacetlyated smooth muscle tropomyosin however binds strongly  to F-actin (Cho & Hitchcock-DeGregori, 1991).  The requirement for N-terminus acetylation of striated muscle tropomyosin for F-actin binding can be overcome by the incorporation of the dipeptide Alanine-serine at the N-terminus ().  For smooth muscle tropomyosin other important residues include the carboxyterminal Glu276 and Thr277 (Cho, 2000).  Like striated muscle tropomyosin the gene product of the Saccharomyces Tpm1 gene requires acetylation to bind actin (Singer & Shaw, 2003).  Saccharomyces tropomyosin Tpm1 requires the cooperation of two gene products, Nat3p, acetyl transferase and Mdm20p (Singer & Shaw, 2003).

Intracellular Localization

Tropomyosin was one of the first actin-binding proteins to be studied by indirect immunofluorescence (Jorgensen et al, 1975; Osborn & Weber, 1979).  It is primarily localised (as one might anticipate) along the actin filaments but is excluded from the leading edge of moving cells (DesMarais et al, 2002; Cooper, 2002) in line with their anti- ADF/Cofilin (Bernstein & Bamburg, 1982) and Arp2/3 complex activities (Blanchoin et al, 2001). 


Competition with other Actin-Binding Proteins.

In addition to controlling myosin interaction with actin filaments tropomyosins may alter binding of calponin (Childs & Watson, 1992), gelsolin (Ishikawa et al, 1989b) , ADF/cofilins (Bernstein & Bamburg, 1982; Nishida et al, 1985; Maciver et al, 1991), MAP2 (Okagaki & Asakura, 1987).


Other Tropomyosin-Binding Proteins

A variety of proteins have been reported to bind tropomyosins.  These studies have been biochemically and/or yeast two hybrid based.  Their physiological significance has not always been readily explicable.

Protein Function Regulation  Reference
Calponin Childs & Watson, 1992
CEACAM1 Adhesion protein   Schumann et al, 2001
Endostatin MacDonald et al, 2001
Enigma LIM  Guy et al, 1999
Gelsolin (sub-domain 2) To regulate gelsolin severing function?  Ca2+ and pH Koepf & Burtnick 1992, 1993; Maciver et al, 2000
S100A2 Gimona, et al, 1997
Table 1.  Tropomyosin binding proteins

Regulation of Muscle Contraction by Tropomyosins.

Contraction of muscle and its the influence of tropomyosin was inferred early (Ebashi, 1963; Ebashi & Endo, 1968).


Regulation of Tropomyosins

The existence of a tropomyosin kinase activity has been reported (Montgomery & Mak, 1984) but remains poorly characterised.  Regulation by caldesmon through Ca2+/calmodulin. 



Tropomyosins are expressed widely in animal tissues being present in probably all vertebrates.  Their status in lower eukaryotes is less certain.  There are genes in the yeast Saccharomyces cerevisiae and in .  However, despite being studied extensively no tropomyosin-like proteins have been isolated or detected from either Acanthamoeba or Dictyostelium.  No tropomyosin homolog seems present in the now complete Arabidopsis thaliana genome. A tropomyosin-like protein (DivIVA) has been identified in the gram positive bacteria (Edwards et al, 2000) and it is possible that this protein is the ancestral tropomyosin.


Tropomyosins and Human Disease

Oncogenic Transformation.  Mutations (), deletions of tropomyosin genes and the altered expression of tropomyosin genes (Hendricks & Weintraub, 1981; Lin et al, 1984; Leavitt et al, 1986; Prasad et al, 1993; Miyado et al, 1996; Lin et al, 2002) have often been reported to be associated with transformation of vertebrate cells and further that over-expressed of normal tropomyosin can inhibit transformation (Prasad et al, 1993) yet it seems that in some cases at least this is due to the 3' untranslated region of the gene (Rastinejad et al, 1993). Janssen & Mier 1997).  The oncogene Ras has been implicated in tropomyosin mediated cell transformation that has in turn been associated with actin cytoskeleton alteration. Forced expression of Tm1 suppresses neoplastic growth characteristics of ras transformed cells through an uncertain mechanism (Prasad et al, 1993). There are some suggestions that anchorage-dependence of growth may be involved (Boyd et al, 1996). 

The role in allergy.  Allergies such as asthma seem to be increasingly common problem for no obvious reason. Many other allergies are caused by reactivity against cytoskeletal proteins.  An example of this is that many hay fever sufferers produce a response to profilin from the pollen of many plants (see profilin).  Tropomyosins too are implicated 

Hypertrophic Cardiomyopathy.  Hypertrophic cardiomyopathy (HCM) is usually an inherited disorder caused by mutations in a number of cardiac cytoskeletal proteins including myosin II heavy chain, troponin T and tropomyosin (Van Driest et al, 2002a b).

Nemaline Myopathy.


Tropomyosin-Like proteins

Several proteins possess regions similar to tropomyosins (Table 2).

TM30nm Miyado et al, 1994

Purification of Tropomyosins from cells and tissues.

Tropomyosins are soluble in neutral to low pH buffers.  Purification of tropomyosin from platelets (Cote & Smillie, 1981). From fibroblasts (Lin et al, 1985; Matsumara  & Yamashiro-Matsumura, 1985)



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