Tau differentially regulates the transport of early endosomes and lysosomes.
Tau differentially regulates the transport of early endosomes and lysosomes.
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DOI：
10.1091/mbc.e22-01-0018
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发表时间：
2022-11-01
影响因子：
3.3
通讯作者：
Hendricks, Adam G.
中科院分区：
文献类型：
--
作者：
Balabanian, Linda;Lessard, Dominique, V;Swaminathan, Karthikeyan;Yaninska, Pamela;Sebastien, Muriel;Wang, Samuel;Stevens, Piper W.;Wiseman, Paul W.;Berger, Christopher L.;Hendricks, Adam G.
微管相关蛋白(MAPs)调节运动蛋白和动力蛋白沿微管的运动，从而控制囊泡和细胞器的运输。神经元MAP tau抑制依赖于动蛋白的运输。酪氨酸激酶使Tyr-18处的tau磷酸化，导致对kinesin-1的抑制作用减弱。我们在表达野生型(WT)tau和拟磷脂型Y18E tau的细胞中检测了早期内小体和溶酶体的运动性。我们量化了tau表达水平对运动性的影响。溶酶体的运动被tau强烈抑制。Y18E tau优先抑制细胞外围的溶酶体，而位于中心的溶酶体受影响较小。早期内体对tau比溶酶体更敏感，并被WT和Y18E tau抑制。我们的结果表明，不同的货物对tau的反应是不同的，这可能是由驱动它们运输的Kinesin马达的类型决定的。在这个模型中，kinesin-1和kinesin-3被tau强烈抑制，而kinesin-2和dynein受影响较小。与Kinesin-1相反，我们发现Kinesin-3被磷酸化的tau强烈抑制。
Microtubule-associated proteins (MAPs) modulate the motility of kinesin and dynein along microtubules to control the transport of vesicles and organelles. The neuronal MAP tau inhibits kinesin-dependent transport. Phosphorylation of tau at Tyr-18 by fyn kinase results in weakened inhibition of kinesin-1. We examined the motility of early endosomes and lysosomes in cells expressing wild-type (WT) tau and phosphomimetic Y18E tau. We quantified the effects on motility as a function of the tau expression level. Lysosome motility is strongly inhibited by tau. Y18E tau preferentially inhibits lysosomes in the cell periphery, while centrally located lysosomes are less affected. Early endosomes are more sensitive to tau than lysosomes and are inhibited by both WT and Y18E tau. Our results show that different cargoes have disparate responses to tau, likely governed by the types of kinesin motors driving their transport. In support of this model, kinesin-1 and -3 are strongly inhibited by tau while kinesin-2 and dynein are less affected. In contrast to kinesin-1, we find that kinesin-3 is strongly inhibited by phosphorylated tau.