Human myosin VIIa is a very slow processive motor protein on various cellular actin structures.

ABSTRACT: Human myosin VIIa (MYO7A) is an actin-linked motor protein associated with human Usher syndrome (USH) type 1B, which causes human congenital hearing and visual loss. Although it has been thought that the role of human myosin VIIa is critical for USH1 protein tethering with actin and transportation along actin bundles in inner-ear hair cells, myosin VIIa's motor function remains unclear. Here, we studied the motor function of the tail-truncated human myosin VIIa dimer (HM7A?Tail/LZ) at the single-molecule level. We found that the HM7A?Tail/LZ moves processively on single actin filaments with a step size of 35 nm. Dwell-time distribution analysis indicated an average waiting time of 3.4 s, yielding ?0.3 s^-1 for the mechanical turnover rate; hence, the velocity of HM7A?Tail/LZ was extremely slow, at 11 nm·s^-1 We also examined HM7A?Tail/LZ movement on various actin structures in demembranated cells. HM7A?Tail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7A?Tail/LZ frequently missed steps on actin tracks and exhibited bidirectional movement at stress fibers, which was not observed with tail-truncated myosin Va. These results suggest that the movement of the human myosin VIIa motor protein is more efficient on lamellipodial and filopodial actin tracks than on stress fibers, which are composed of actin filaments with different polarity, and that the actin structures influence the characteristics of cargo transportation by human myosin VIIa. In conclusion, myosin VIIa movement appears to be suitable for translocating USH1 proteins on stereocilia actin bundles in inner-ear hair cells.

SUBMITTER: Sato O 

PROVIDER: S-EPMC5491779 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature