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 Yengo, Bechara Kachar

Research output: Contribution to journalArticle

36 Citations (Scopus)

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

Fingerprint

Myosins
myosin
actin
Actins
pseudopodia
Pseudopodia
tail
Stereocilia
Myosin Type III
hearing
microfilaments
Actin Cytoskeleton
Hearing Loss
Audition
polymerization
binding sites
Binding Sites
cells
Phenotype
mutation

All Science Journal Classification (ASJC) codes

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

Cite this

Merritt, R. C., Manor, U., Salles, F. T., Grati, MH., Dose, A. C., Unrath, W. C., ... 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
Merritt, Raymond C. ; Manor, Uri ; Salles, Felipe T. ; Grati, M'Hamed ; Dose, Andrea C. ; Unrath, William C. ; Quintero, Omar A. ; Yengo, Christopher ; Kachar, Bechara. / Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions. In: Current Biology. 2012 ; Vol. 22, No. 4. pp. 320-325.
@article{132418203e4e4d58980cad49a1157c41,
title = "Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions",
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.",
author = "Merritt, {Raymond C.} and Uri Manor and Salles, {Felipe T.} and M'Hamed Grati and Dose, {Andrea C.} and Unrath, {William C.} and Quintero, {Omar A.} and Christopher Yengo and Bechara Kachar",
year = "2012",
month = "2",
day = "21",
doi = "10.1016/j.cub.2011.12.053",
language = "English (US)",
volume = "22",
pages = "320--325",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "4",

}

Merritt, RC, Manor, U, Salles, FT, Grati, MH, Dose, AC, Unrath, WC, Quintero, OA, Yengo, C & Kachar, B 2012, 'Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions', Current Biology, vol. 22, no. 4, pp. 320-325. https://doi.org/10.1016/j.cub.2011.12.053

Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions. / Merritt, Raymond C.; Manor, Uri; Salles, Felipe T.; Grati, M'Hamed; Dose, Andrea C.; Unrath, William C.; Quintero, Omar A.; Yengo, Christopher; Kachar, Bechara.

In: Current Biology, Vol. 22, No. 4, 21.02.2012, p. 320-325.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Myosin IIIB uses an actin-binding motif in its espin-1 cargo to reach the tips of actin protrusions

AU - Merritt, Raymond C.

AU - Manor, Uri

AU - Salles, Felipe T.

AU - Grati, M'Hamed

AU - Dose, Andrea C.

AU - Unrath, William C.

AU - Quintero, Omar A.

AU - Yengo, Christopher

AU - Kachar, Bechara

PY - 2012/2/21

Y1 - 2012/2/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84857356790&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857356790&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2011.12.053

DO - 10.1016/j.cub.2011.12.053

M3 - Article

C2 - 22264607

AN - SCOPUS:84857356790

VL - 22

SP - 320

EP - 325

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 4

ER -