Impact of the Motor and Tail Domains of Class III Myosins on Regulating the Formation and Elongation of Actin Protrusions

J Biol Chem. 2016 Oct 21;291(43):22781-22792. doi: 10.1074/jbc.M116.733741. Epub 2016 Aug 31.


Class III myosins (MYO3A and MYO3B) are proposed to function as transporters as well as length and ultrastructure regulators within stable actin-based protrusions such as stereocilia and calycal processes. MYO3A differs from MYO3B in that it contains an extended tail domain with an additional actin-binding motif. We examined how the properties of the motor and tail domains of human class III myosins impact their ability to enhance the formation and elongation of actin protrusions. Direct examination of the motor and enzymatic properties of human MYO3A and MYO3B revealed that MYO3A is a 2-fold faster motor with enhanced ATPase activity and actin affinity. A chimera in which the MYO3A tail was fused to the MYO3B motor demonstrated that motor activity correlates with formation and elongation of actin protrusions. We demonstrate that removal of individual exons (30-34) in the MYO3A tail does not prevent filopodia tip localization but abolishes the ability to enhance actin protrusion formation and elongation in COS7 cells. Interestingly, our results demonstrate that MYO3A slows filopodia dynamics and enhances filopodia lifetime in COS7 cells. We also demonstrate that MYO3A is more efficient than MYO3B at increasing formation and elongation of stable microvilli on the surface of cultured epithelial cells. We propose that the unique features of MYO3A, enhanced motor activity, and an extended tail with tail actin-binding motif, allow it to play an important role in stable actin protrusion length and ultrastructure maintenance.

Keywords: actin; cytoskeleton; hair cell; molecular motor; myosin.

MeSH terms

  • Actins / genetics
  • Actins / metabolism*
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • Myosin Heavy Chains / genetics
  • Myosin Heavy Chains / metabolism*
  • Myosin Type III / genetics
  • Myosin Type III / metabolism*
  • Pseudopodia / genetics
  • Pseudopodia / metabolism*


  • Actins
  • MYO3B protein, human
  • MYO3A protein, human
  • Myosin Type III
  • Myosin Heavy Chains