ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum.
ULK4 and Fused/STK36 interact to mediate assembly of a motile flagellum.
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DOI：
10.1091/mbc.e22-06-0222
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发表时间：
2023-06-01
影响因子：
3.3
通讯作者：
Gluenz, Eva
中科院分区：
文献类型：
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作者：
McCoy, Ciaran J.;Paupelin-Vaucelle, Humbeline;Gorilak, Peter;Beneke, Tom;Varga, Vladimir;Gluenz, Eva
unc -51样激酶（ULK）家族丝氨酸-苏氨酸蛋白激酶同源物与多种物种的运动纤毛功能有关。小鼠中Fused/STK36和ULK4的突变导致脑积水和其他与纤毛缺陷一致的表型。这两种蛋白质如何参与运动纤毛的组装和功能尚不清楚。本文研究了鞭毛原生利什曼原虫ULK4和融合基因敲除（KO）突变体的表型。两种KO突变体都表现出鞭毛细胞骨架的各种结构缺陷。生化方法表明这些蛋白在空间上接近，并表明LmxULK4和LmxFused的n端之间存在直接相互作用。这两种蛋白在整个细胞体和鞭毛上都表现出分散的定位，在鞭毛基部和尖端附近富集。LmxULK4的稳定表达依赖于LmxFused的存在。熔融/STK36先前被证明定位于哺乳动物的运动纤毛，我们在这里证明ULK4也定位于小鼠室管膜细胞的运动纤毛。综上所述，这些数据表明假激酶ULK4在运动纤毛稳定组装所需的途径中是激酶Fused/ STK36的正调节因子。
Unc-51–like kinase (ULK) family serine–threonine protein kinase homologues have been linked to the function of motile cilia in diverse species. Mutations in Fused/STK36 and ULK4 in mice resulted in hydrocephalus and other phenotypes consistent with ciliary defects. How either protein contributes to the assembly and function of motile cilia is not well understood. Here we studied the phenotypes of ULK4 and Fused gene knockout (KO) mutants in the flagellated protist Leishmania mexicana. Both KO mutants exhibited a variety of structural defects of the flagellum cytoskeleton. Biochemical approaches indicate spatial proximity of these proteins and indicate a direct interaction between the N-terminus of LmxULK4 and LmxFused. Both proteins display a dispersed localization throughout the cell body and flagellum, with enrichment near the flagellar base and tip. The stable expression of LmxULK4 was dependent on the presence of LmxFused. Fused/STK36 was previously shown to localize to mammalian motile cilia, and we demonstrate here that ULK4 also localizes to the motile cilia in mouse ependymal cells. Taken together these data suggest a model where the pseudokinase ULK4 is a positive regulator of the kinase Fused/ STK36 in a pathway required for stable assembly of motile cilia.
通过 Fused 的二聚化和 Cubitus Interruptus 的核转位来转导 Hedgehog 信号
影响因子：
44.1
作者：
通讯作者：
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