title: Load-dependent modulation of non-muscle myosin-2A function by tropomyosin 4.2.
abstract: Tropomyosin isoforms play an important role in the organisation of cytoplasmic actomyosin complexes in regard to function and cellular localisation. In particular, Tpm4.2 is upregulated in rapidly migrating cells and responsible for the specific recruitment of the cytoplasmic class-2 myosin NM-2A to actin filaments during the formation of stress fibres. Here, we investigate how the decoration of F-actin with Tpm4.2 affects the motor properties of NM-2A under conditions of low and high load. In the absence of external forces, decoration of actin filaments with Tpm4.2 does not affect the gated release of ADP from NM-2A and the transition from strong to weak actin-binding states. In the presence of resisting loads, our results reveal a marked increase in the mechanosensitive gating between the leading and trailing myosin head. Thereby, the processive behaviour of NM-2A is enhanced in the presence of resisting loads. The load- and Tpm4.2-induced changes in the functional behaviour of NM-2A are in good agreement with the role of this myosin in the context of stress fibres and the maintenance of cellular tension.
authors: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Nikolas
authors: N
authors: Hundt
authors: Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Walter
authors: W
authors: Steffen
authors: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Salma
authors: S
authors: Pathan-Chhatbar
authors: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Manuel H
authors: MH
authors: Taft
authors: Institute for Biophysical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.|Division for Structural Analysis, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors: Dietmar J
authors: DJ
authors: Manstein
mesh_terms: D000199:Actins / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D014335:Tropomyosin / Q000378:metabolism*
chemical_list: D000199:Actins; D020033:Protein Isoforms; C501213:TPM4 protein, human; D014335:Tropomyosin; D000244:Adenosine Diphosphate; D024507:Nonmuscle Myosin Type IIA