Myosin Vc Is Specialized for Transport on a Secretory Superhighway

A hallmark of the well-studied vertebrate class Va myosin is its ability to take multiple steps on actin as a single molecule without dissociating, a feature called “processivity.” Therefore, it was surprising when kinetic and single-molecule assays showed that human myosin Vc (MyoVc) was not processive on single-actin filaments [1–3]. We explored the possibility that MyoVc is processive only under conditions that resemble its biological context. Recently, it was shown that zymogen vesicles are transported on actin “superhighways” composed of parallel actin cables nucleated by formins from the plasma membrane [4]. Loss of these cables compromises orderly apical targeting of vesicles. MyoVc has been implicated in transporting secretory vesicles to the apical membrane [5]. We hypothesized that actin cables regulate the processive properties of MyoVc. We show that MyoVc is unique in taking variable size steps, which are frequently in the backward direction. Results obtained with chimeric constructs implicate the lever arm/rod of MyoVc as being responsible for these properties. Actin bundles allow single MyoVc motors to move processively. Remarkably, even teams of MyoVc motors require actin bundles to move continuously at physiological ionic strength. The irregular stepping pattern of MyoVc, which may result from flexibility in the lever arm/rod of MyoVc, appears to be a unique structural adaptation that allows the actin track to spatially restrict the activity of MyoVc to specialized actin cables in order to co-ordinate and target the final stages of vesicle secretion. •Myosin Vc does not move processively on single actin filaments•The unloaded stepping pattern of myosin Vc is irregular with numerous back steps•The lever arm and/or rod of myosin Vc is responsible for “sloppy” stepping•Single and multiple myosin Vc motors require actin cables for continuous motion Sladewski et al. show that the actin track regulates the ability of myosin Vc to transport cargo. The irregular step size and frequent back steps of myosin Vc restrict motion to actin bundles, consistent with in vivo trafficking of exocrine secretory granules being targeted to newly discovered actin cables built at the cellular apical surface.