Non-muscle tropomyosins inhibit myosin-19 and dynamically localize to mitochondrially associated actin filaments

Cameron P Thompson1, Luther W Pollard2, Mengqi Xu1

  • 1Department of Physiology and Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Insights

Tropomyosin 3.1 (Tpm3.1) and 1.7 (Tpm1.7) inhibit the actin-binding motor Myosin-19 (Myo19). This regulation occurs dynamically near mitochondria, suggesting a mechanism for controlling mitochondrial function.

Area of Science:

  • Cell Biology
  • Molecular Motors
  • Mitochondrial Dynamics

Background:

  • Myosin-19 (Myo19) is a crucial motor protein for maintaining mitochondrial homeostasis and mitochondrial-endoplasmic reticulum (mitoER) contact sites.
  • Understanding Myo19 regulation is vital for mitochondrial health, yet regulatory mechanisms remain largely unknown.

Purpose of the Study:

  • To investigate the potential role of non-muscle tropomyosins in regulating Myo19 activity.
  • To elucidate how tropomyosin isoforms interact with Myo19 and actin filaments.

Main Methods:

  • In vitro actin filament gliding assays to assess Myo19-actin interactions.
  • Cellular localization studies using HeLa cells to observe Tropomyosin 3.1 (Tpm3.1) dynamics near mitochondria.

Main Results:

  • Tropomyosin 3.1 (Tpm3.1) and Tropomyosin 1.7 (Tpm1.7) cooperatively inhibit Myo19's interaction with F-actin, causing an all-or-none stalling effect.
  • Tpm3.1 localizes to actin filaments near mitochondria in HeLa cells and dynamically interacts with mitochondrially-associated actin waves.

Conclusions:

  • Tropomyosin isoforms Tpm3.1 and Tpm1.7 act as negative regulators of Myo19.
  • This tropomyosin-based regulation provides spatial and dynamic control over Myo19 activity, impacting mitochondrial function.

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