Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP.
Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP.
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DOI：
10.1038/srep08238
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发表时间：
2015-02-04
影响因子：
4.6
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Ishida M;Ohbayashi N;Fukuda M
黑素小体是黑素细胞中与溶酶体相关的细胞器，通过双向(顺行和逆行)微管运输和单向肌动蛋白依赖运输的协调，从核周运输到细胞外围。虽然调控肌动蛋白逆行转运和肌动蛋白依赖性转运的分子机制已经被发现，但对哺乳动物细胞微管上的顺行转运复合体知之甚少。在这里，我们发现黑素小体上的小GTP酶Rab1a招募Skip/PLEKHM2作为Rab1a的特异性效应器，Rab1a、Skip和一个Kinesin-1/(Kif5b+KLC2)马达形成一个运输复合体，介导黑素细胞的顺行黑素小体运输。有趣的是，Ar18，Arf样的小GTP酶也与SKIP相互作用，特异性地定位于溶酶体，并调节它们在黑素细胞中的顺行运输。我们的发现表明，依赖于微管的黑素体和溶酶体的顺行运输分别受到独立的Cargo受体，即Rab1a和Ar18的不同调节，但跳跃-Kinesin-1机制负责这两种物质的运输。
Melanosomes are lysosome-related organelles in melanocytes that are transported from the perinucleus to the cell periphery by coordination between bidirectional (anterograde and retrograde) microtubule-dependent transport and unidirectional actin-dependent transport. Although the molecular machineries that mediate retrograde transport and actin-dependent transport have already been identified, little is known about the anterograde transport complex on microtubules in mammalian cells. Here we discovered that small GTPase Rab1A on melanosomes recruits SKIP/PLEKHM2 as a Rab1A-specific effector and that Rab1A, SKIP, and a kinesin-1/(Kif5b+KLC2) motor form a transport complex that mediates anterograde melanosome transport in melanocytes. Interestingly, Arl8, Arf-like small GTPase that also interacts with SKIP, is specifically localized at lysosomes and regulates their anterograde transport in melanocytes. Our findings suggest that the anterograde microtubule-dependent transport of melanosomes and lysosomes are differently regulated by independent cargo receptors, i.e., Rab1A and Arl8, respectively, but that a SKIP–kinesin-1 mechanism is responsible for the transport of both.
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