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

• Published in: Nature 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
• Language: English
• 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
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb1851

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.