The unconventional myosin-VIIa associates with lysosomes.
The unconventional myosin-VIIa associates with lysosomes.
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DOI：
10.1002/cm.20080
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发表时间：
2005-09
影响因子：
--
通讯作者：
Lily E Soni;C. Warren;C. Bucci;D. Orten;T. Hasson
中科院分区：
文献类型：
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作者：
Lily E Soni;C. Warren;C. Bucci;D. Orten;T. Hasson
肌球蛋白VIIa（MYO 7a）基因突变导致人类Usher病，其特征为听力障碍和进行性视网膜变性。在视网膜中，肌球蛋白VIIa在视网膜色素上皮中高度表达，它在黑素体和其他消化细胞器的定位中发挥作用。使用人培养的视网膜色素上皮细胞系，ARPE-19，作为一个模型系统，我们发现，一个人口的肌球蛋白-VIIa与组织蛋白酶D和Rab 7阳性溶酶体。肌球蛋白-VIIa与溶酶体的关联是Rab 7独立的，因为Rab 7的显性阴性和显性活性版本不破坏肌球蛋白-VIIa向溶酶体的募集。肌球蛋白-VIIa与溶酶体的协会也是独立的肌动蛋白和微管细胞骨架。肌球蛋白-VIIa与溶酶体在密度梯度上共纯化，分馏和提取实验表明，它与溶酶体表面紧密相关。这些研究表明，肌球蛋白VIIa是一个溶酶体马达。
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.