Myosin VI is an actin-based motor that moves backwards

Abstract

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.

The MYO6 interactome reveals adaptor complexes coordinating early endosome and cytoskeletal dynamics

“…The myosin superfamily can be grouped into at least 35 different classes, which all translocate towards the plus‐end of actin filaments with the exception of MYO6 1. The unique directionality of MYO6 facilitates its specific cellular roles in endocytosis, receptor trafficking, protein secretion and autophagy.…”

Controllable molecular motors engineered from myosin and RNA

“…3 and Supplementary Movie 3c). The lever arm orientation of myosin VI differs between the ADP and nucleotide-free states, swinging through a small angle that represents a substep of the larger power stroke 29,30 . We observed this reorientation when comparing reconstructions of the hybrid motor in the ADP and nucleotide-free states, as expected for a functional engineered lever arm (Fig.…”

Myosin VI small insert isoform maintains exocytosis by tethering secretory granules to the cortical actin

“…3 B), lacking the ability to interact with actin (Mermall et al, 1998;Wells et al, 1999;Krendel and Mooseker, 2005), should alter the behavior of SGs at the plasma membrane by acting in a dominant-negative manner. PC12 cells coexpressing NPY-mCherry with either GFP (control), GFP-MyoVI-SIfull, GFP-MyoVI-NIfull, GFP-myosin VI SI tail (GFP-MyoVI-SItail), or GFP-myosin VI NI tail (GFP-MyoVINItail) were imaged by TIRF microscopy (Fig.…”

“…Myosin VI is the only myosin that moves toward the minus end of actin filaments (Wells et al, 1999) and, in association with specific binding partners, functions in endocytosis, cell under milder levels of c-Src activity (Fig. S5 A).…”

“…One of the identified proteins was myosin VI. This motor protein is unique as, in addition to playing an important anchoring role (Self et al, 1999), its directionality along actin filaments runs counter to other myosin proteins (Wells et al, 1999;Bryant et al, 2007). Four alternatively spliced isoforms of myosin VI have been identified containing either a large insert (21-31 aa), a small insert (SI; 9 aa), no insert (NI), or both inserts within the C-terminal tail, located in the cargobinding domain (Buss et al, 2001;Au et al, 2007).…”