A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus

Ryutaro Shirakawa, Sakurako Goto-Ito, Kota Goto, Shonosuke Wakayama, Haremaru Kubo, Natsumi Sakata, Duc Anh Trinh, Atsushi Yamagata, Yusuke Sato, Hiroshi Masumoto, Jinglei Cheng, Toyoshi Fujimoto, Shuya Fukai, Hisanori Horiuchi

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2 Citations (Scopus)

Abstract

Protein prenylation is essential for many cellular processes including signal transduction, cytoskeletal reorganization, and membrane trafficking. Here, we identify a novel type of protein prenyltransferase, which we named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the β subunit of RabGGTase. Using a biotinylated geranylgeranyl analogue, we identified the Golgi SNARE protein Ykt6 as a substrate of GGTase-III. GGTase-III transfers a geranylgeranyl group to mono-farnesylated Ykt6, generating doubly prenylated Ykt6. The crystal structure of GGTase-III in complex with Ykt6 provides structural basis for Ykt6 double prenylation. In GGTase-III-deficient cells, Ykt6 remained in a singly prenylated form, and the Golgi SNARE complex assembly was severely impaired. Consequently, the Golgi apparatus was structurally disorganized, and intra-Golgi protein trafficking was delayed. Our findings reveal a fourth type of protein prenyltransferase that generates geranylgeranyl-farnesyl Ykt6. Double prenylation of Ykt6 is essential for the structural and functional organization of the Golgi apparatus.

Original languageEnglish
Article numbere104120
JournalEMBO Journal
Volume39
Issue number8
DOIs
Publication statusPublished - 2020 Apr 15

Keywords

  • Golgi
  • PTAR1
  • SNARE
  • Ykt6
  • protein prenylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Shirakawa, R., Goto-Ito, S., Goto, K., Wakayama, S., Kubo, H., Sakata, N., Trinh, D. A., Yamagata, A., Sato, Y., Masumoto, H., Cheng, J., Fujimoto, T., Fukai, S., & Horiuchi, H. (2020). A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus. EMBO Journal, 39(8), [e104120]. https://doi.org/10.15252/embj.2019104120