Myosin IIIa boosts elongation of stereocilia by transporting espin 1 to the plus ends of actin filaments

Two proteins implicated in inherited deafness, myosin IIIa, a plus-end-directed motor, and espin, an actin-bundling protein containing the actin-monomer-binding motif WH2, have been shown to influence the length of mechanosensory stereocilia. Here we report that espin 1, an ankyrin repeat-containing...

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Published inNature cell biology Vol. 11; no. 4; pp. 443 - 450
Main Authors Yengo, Christopher M, Kachar, Bechara, Merritt, Raymond C, Sousa, Aurea D, Salles, Felipe T, Manor, Uri, Dougherty, Gerard W, Moore, Judy E, Dosé, Andréa C
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.04.2009
Nature Publishing Group
Subjects
Actin
Actin Cytoskeleton - metabolism
Actin Cytoskeleton - ultrastructure
Animals
Ankyrin Repeat
Biological transport
Biomedical and Life Sciences
Cancer Research
Cell Biology
Cellular control mechanisms
Chlorocebus aethiops
Cilia - metabolism
Cilia - ultrastructure
COS Cells
Developmental Biology
Genetic aspects
letter
Life Sciences
Mice
Microfilament Proteins - chemistry
Microfilament Proteins - metabolism
Myosin
Myosin Type III - metabolism
Physiological aspects
Physiology
Protein Binding
Protein Transport
Proteins
Pseudopodia - metabolism
Pseudopodia - ultrastructure
Rats
Stem Cells
Transfection
United States
Italy
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Summary:Two proteins implicated in inherited deafness, myosin IIIa, a plus-end-directed motor, and espin, an actin-bundling protein containing the actin-monomer-binding motif WH2, have been shown to influence the length of mechanosensory stereocilia. Here we report that espin 1, an ankyrin repeat-containing isoform of espin, colocalizes with myosin IIIa at stereocilia tips and interacts with a unique conserved domain of myosin IIIa. We show that combined overexpression of these proteins causes greater elongation of stereocilia, compared with overexpression of either myosin IIIa alone or espin 1 alone. When these two proteins were co-expressed in the fibroblast-like COS-7 cell line they induced a tenfold elongation of filopodia. This extraordinary filopodia elongation results from the transport of espin 1 to the plus ends of F-actin by myosin IIIa and depends on espin 1 WH2 activity. This study provides the basis for understanding the role of myosin IIIa and espin 1 in regulating stereocilia length, and presents a physiological example where myosins can boost elongation of actin protrusions by transporting actin regulatory factors to the plus ends of actin filaments.
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Author Contributions: R.C.M. designed probes and experiments, performed the GST pull-downs, cell culture, immunocytochemistry, and transfections; F.T.S. performed the dissections, cell and organotypic cultures, immuno-histochemistry, transfections, and confocal imaging; G.W.D. and A.C.D. designed probes, performed transfections, and contributed to experimental design; U.M. performed image and statistical analyses; A.D.S. characterized antibody and DNA probes; C.M.Y. and J.E.M. generated myosin IIIa kinase dead cDNA, purified, and performed kinase and motor activity assays.; B.K. performed electron microscopy, designed experiments, and analyzed the results together with all the other authors. All authors discussed and helped prepare the manuscript.
Current address: Consorzio Mario Negri Sud, Department of Cell Biology and Oncology, Santa Maria Imbaro, Chieti, Italy 66030.
Contributed equally
ISSN:1465-7392
1476-4679
DOI:10.1038/ncb1851