Distinct sites in tropomyosin specify shared and isoform-specific regulation of myosins II and V

Cytoskeleton (Hoboken). 2018 Apr;75(4):150-163. doi: 10.1002/cm.21440. Epub 2018 Mar 26.


Muscle contraction, cytokinesis, cellular movement, and intracellular transport depend on regulated actin-myosin interaction. Most actin filaments bind one or more isoform of tropomyosin, a coiled-coil protein that stabilizes the filaments and regulates interactions with other actin-binding proteins, including myosin. Isoform-specific allosteric regulation of muscle myosin II by actin-tropomyosin is well-established while that of processive myosins, such as myosin V, which transport organelles and macromolecules in the cell periphery, is less certain. Is the regulation by tropomyosin a universal mechanism, the consequence of the conserved periodic structures of tropomyosin, or is it the result of specialized interactions between particular isoforms of myosin and tropomyosin? Here, we show that striated muscle tropomyosin, Tpm1.1, inhibits fast skeletal muscle myosin II but not myosin Va. The non-muscle tropomyosin, Tpm3.1, in contrast, activates both myosins. To decipher the molecular basis of these opposing regulatory effects, we introduced mutations at conserved surface residues within the six periodic repeats (periods) of Tpm3.1, in positions homologous or analogous to those important for regulation of skeletal muscle myosin by Tpm1.1. We identified conserved residues in the internal periods of both tropomyosin isoforms that are important for the function of myosin Va and striated myosin II. Conserved residues in the internal and C-terminal periods that correspond to Tpm3.1-specific exons inhibit myosin Va but not myosin II function. These results suggest that tropomyosins may directly impact myosin function through both general and isoform-specific mechanisms that identify actin tracks for the recruitment and function of particular myosins.

Keywords: actin cytoskeleton; actomyosin regulation; coiled coil; intracellular transport; muscle contraction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cell Movement*
  • Chickens
  • Mice
  • Myosin Type II / chemistry
  • Myosin Type II / metabolism*
  • Myosin Type V / chemistry
  • Myosin Type V / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Isoforms
  • Rats
  • Sequence Homology
  • Tropomyosin / chemistry
  • Tropomyosin / metabolism*


  • Actins
  • Protein Isoforms
  • Tropomyosin
  • Myosin Type II
  • Myosin Type V