The unconventional myosin-VIIa associates with lysosomes

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Abstract
Mutations in the myosin‐VIIa (MYO7a) gene cause human Usher disease, characterized by hearing impairment and progressive retinal degeneration. In the retina, myosin‐VIIa is highly expressed in the retinal pigment epithelium, where it plays a role in the positioning of melanosomes and other digestion organelles. Using a human cultured retinal pigmented epithelia cell line, ARPE‐19, as a model system, we have found that a population of myosin‐VIIa is associated with cathepsin D‐ and Rab7‐positive lysosomes. Association of myosin‐VIIa with lysosomes was Rab7 independent, as dominant negative and dominant active versions of Rab7 did not disrupt myosin‐VIIa recruitment to lysosomes. Association of myosin‐VIIa with lysosomes was also independent of the actin and microtubule cytoskeleton. Myosin‐VIIa copurified with lysosomes on density gradients, and fractionation and extraction experiments suggested that it was tightly associated with the lysosome surface. These studies suggest that myosin‐VIIa is a lysosome motor. Cell Motil. Cytoskeleton 62:13–26, 2005.