期刊
JOURNAL OF CELL SCIENCE
卷 135, 期 5, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258566
关键词
TMEM55A; TMEM55B; S-palmitoylation; Lysosomal positioning; Acyl-RAC
类别
资金
- Deutsche Forschungsgemeinschaft (DFG) [SA 683/9-1, FOR2625, DA 1785/2-1, DA 1785/2-2]
The spatiotemporal cellular distribution of lysosomes relies on active transport driven by microtubule proteins. TMEM55B and TMEM55A are S-palmitoylated proteins that play a critical role in lysosomal positioning and sorting.
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 molecularmotors 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 tomodulate 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.
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