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 (HM7AΔTail/LZ) at the single-molecule level. We found that the HM7AΔTail/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 HM7AΔTail/LZ was extremely slow, at 11 nm·s-1 We also examined HM7AΔTail/LZ movement on various actin structures in demembranated cells. HM7AΔTail/LZ showed unidirectional movement on actin structures at cell edges, such as lamellipodia and filopodia. However, HM7AΔTail/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.

• Authors: Osamu Sato, Satoshi Komatsu, Tsuyoshi Sakai, Yoshikazu Tsukasaki, Ryosuke Tanaka, Takeomi Mizutani, Tomonobu M Watanabe, Reiko Ikebe, Mitsuo Ikebe
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 292 Issue 26 Pg. 10950-10960 (06 30 2017) ISSN: 1083-351X [Electronic] United States
• PMID: 28507101 (Publication Type: Journal Article)
• Copyright: © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Actins
• MYO7A protein, human
• Myo7a protein, mouse
• Myosin VIIa
• MYO5A protein, human
• Myosin Type V
• Myosin Heavy Chains
• Myosins

Topics

• 3T3 Cells
• Actins (genetics, metabolism)
• Amino Acid Sequence
• Animals
• Humans
• Mice
• Myosin Heavy Chains (genetics, metabolism)
• Myosin Type V (genetics, metabolism)
• Myosin VIIa
• Myosins (genetics, metabolism)
• Protein Transport (genetics)
• Pseudopodia (genetics, metabolism)
• Sequence Deletion
• Usher Syndromes (genetics, metabolism)