The unconventional myosin-VIIa associates with lysosomes.
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.
Section of Cell and Developmental Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093-0368, USA.
Lily E
LE
Soni
Carmen M
CM
Warren
Cecilia
C
Bucci
Dana J
DJ
Orten
Tama
T
Hasson
D002402:Cathepsin D / Q000378:metabolism; D002458:Cell Fractionation; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism*; D020409:Molecular Motor Proteins / Q000378:metabolism*; D000081412:Myosin VIIa; D009218:Myosins / Q000378:metabolism*; D010857:Pigment Epithelium of Eye / Q000166:cytology* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
C000631455:MYO7A protein, human; D020409:Molecular Motor Proteins; D000081412:Myosin VIIa; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D002402:Cathepsin D; D009218:Myosins; D004398:Dyneins; D020691:rab GTP-Binding Proteins