Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions

Raymond C. Merritt, Uri Manor, Felipe T. Salles, M'Hamed Grati, Andrea C. Dose, William C. Unrath, Omar A. Quintero, Christopher M. Yengo, Bechara Kachar

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Myosin IIIA (MYO3A) targets actin protrusion tips using a motility mechanism dependent on both motor and tail actin-binding activity [1]. We show that myosin IIIB (MYO3B) lacks tail actin-binding activity and is unable to target COS7 cell filopodia tips, yet is somehow able to target stereocilia tips. Strikingly, when MYO3B is coexpressed with espin-1 (ESPN1), a MYO3A cargo protein endogenously expressed in stereocilia [2], MYO3B targets and carries ESPN1 to COS7 filopodia tips. We show that this tip localization is lost when we remove the ESPN1 C terminus actin-binding site. We also demonstrate that, like MYO3A [2], MYO3B can elongate filopodia by transporting ESPN1 to the polymerizing end of actin filaments. The mutual dependence of MYO3B and ESPN1 for tip localization reveals a novel mechanism for the cell to regulate myosin tip localization via a reciprocal relationship with cargo that directly participates in actin binding for motility. Our results are consistent with a novel form of motility for class III myosins that requires both motor and tail domain actin-binding activity and show that the actin-binding tail can be replaced by actin-binding cargo. This study also provides a framework to better understand the late-onset hearing loss phenotype in patients with MYO3A mutations.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalCurrent Biology
Volume22
Issue number4
DOIs
StatePublished - Feb 21 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Fingerprint Dive into the research topics of 'Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions'. Together they form a unique fingerprint.

  • Cite this

    Merritt, R. C., Manor, U., Salles, F. T., Grati, MH., Dose, A. C., Unrath, W. C., Quintero, O. A., Yengo, C. M., & Kachar, B. (2012). Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions. Current Biology, 22(4), 320-325. https://doi.org/10.1016/j.cub.2011.12.053