Double prenylation of SNARE protein Ykt6 is required for lysosomal hydrolase trafficking
| Autor: | Natsumi Sakata, Duc Anh Trinh, Ryutaro Shirakawa, Hisanori Horiuchi, Kota Goto |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Hydrolases
Farnesyltransferase Protein Prenylation Golgi Apparatus Cathepsin D Membrane Fusion Biochemistry Rab geranylgeranyltransferase R-SNARE Proteins 03 medical and health sciences symbols.namesake 0302 clinical medicine Prenylation Golgi membrane fusion Animals Humans Molecular Biology 030304 developmental biology G alpha subunit 0303 health sciences Alkyl and Aryl Transferases biology Chemistry General Medicine Golgi apparatus Dimethylallyltranstransferase Cell biology Protein Transport symbols biology.protein Protein prenylation Lysosomes SNARE Proteins 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | The Journal of Biochemistry. 169:363-370 |
| ISSN: | 1756-2651 0021-924X |
| DOI: | 10.1093/jb/mvaa111 |
| Popis: | Ykt6 is an evolutionarily conserved SNARE protein regulating Golgi membrane fusion and other diverse membrane trafficking pathways. Unlike most SNARE proteins, Ykt6 lacks a transmembrane domain but instead has a tandem cysteine motif at the C-terminus. Recently, we have demonstrated that Ykt6 undergoes double prenylation at the C-terminal two cysteines first by farnesyltransferase and then by a newly identified protein prenyltransferase named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of a novel α subunit prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of Rab geranylgeranyltransferase. PTAR1 knockout (KO) cells, where Ykt6 is singly prenylated with a farnesyl moiety, exhibit structural and functional abnormalities in the Golgi apparatus with delayed intra-Golgi trafficking and impaired protein glycosylation. It remains unclear whether the second prenylation of Ykt6 is required for proper trafficking of lysosomal hydrolases from Golgi to lysosomes. Here, we show that lysosomal hydrolases, cathepsin D and β-hexosaminidase, were missorted at the trans-Golgi network and secreted into the extracellular space in PTAR1 KO cells. Moreover, maturation of these hydrolases was disturbed. LC3B, an autophagy marker, was accumulated in PTAR1 KO cells, suggesting defects in cellular degradation pathways. Thus, doubly prenylated Ykt6, but not singly prenylated Ykt6, is critical for the efficient sorting and trafficking of acid hydrolases to lysosomes. |
| Databáze: | OpenAIRE |
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