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S-palmitoylation determines TMEM55B-dependent positioning of lysosomes.
Journal of Cell Science ( IF 3.3 ) Pub Date : 2021-09-07 , DOI: 10.1242/jcs.258566
Sönke Rudnik 1 , Saskia Heybrock 1 , Paul Saftig 1 , Markus Damme 1
Affiliation  

The spatiotemporal cellular distribution of lysosomes depends on active transport mainly driven by microtubule motors such as kinesins and dynein. Different protein complexes attach these molecular motors to their vesicular cargo. TMEM55B (also known as PIP4P1), as an integral lysosomal membrane protein, is a component of such a complex that mediates the retrograde transport of lysosomes by establishing interactions with the cytosolic scaffold protein JIP4 (also known as SPAG9) and dynein-dynactin. Here, we show that TMEM55B and its paralog TMEM55A (PIP4P2) are S-palmitoylated proteins that are lipidated at multiple cysteine residues. Mutation of all cysteines in TMEM55B prevents S-palmitoylation and causes retention of the mutated protein in the Golgi. Consequently, non-palmitoylated TMEM55B is no longer able to modulate lysosomal positioning and the perinuclear clustering of lysosomes. Additional mutagenesis of the dileucine-based lysosomal sorting motif in non-palmitoylated TMEM55B leads to partial missorting to the plasma membrane instead of retention in the Golgi, implicating a direct effect of S-palmitoylation on the adaptor protein-dependent sorting of TMEM55B. Our data suggest a critical role for S-palmitoylation in the trafficking of TMEM55B and TMEM55B-dependent lysosomal positioning.

中文翻译:


S-棕榈酰化决定了溶酶体的 TMEM55B 依赖性定位。



溶酶体的时空细胞分布取决于主要由驱动蛋白和动力蛋白等微管马达驱动的主动运输。不同的蛋白质复合物将这些分子马达附着在它们的囊泡货物上。 TMEM55B(也称为 PIP4P1)作为一种完整的溶酶体膜蛋白,是这种复合物的一个组成部分,通过与胞质支架蛋白 JIP4(也称为 SPAG9)和动力蛋白-动力蛋白建立相互作用来介导溶酶体的逆行转运。在这里,我们证明 TMEM55B 及其旁系同源物 TMEM55A (PIP4P2) 是在多个半胱氨酸残基处脂化的 S-棕榈酰化蛋白。 TMEM55B 中所有半胱氨酸的突变会阻止 S-棕榈酰化并导致突变蛋白保留在高尔基体中。因此,非棕榈酰化 TMEM55B 不再能够调节溶酶体定位和溶酶体的核周聚集。非棕榈酰化 TMEM55B 中基于双亮氨酸的溶酶体分选基序的额外诱变导致部分错配到质膜而不是保留在高尔基体中,这表明 S-棕榈酰化对 TMEM55B 的接头蛋白依赖性分选有直接影响。我们的数据表明 S-棕榈酰化在 TMEM55B 运输和 TMEM55B 依赖性溶酶体定位中发挥关键作用。
更新日期:2021-08-05
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