@article{92f2f5dc716c4d1cacbd390b54136715,
title = "A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus",
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.",
keywords = "Golgi, PTAR1, SNARE, Ykt6, protein prenylation",
author = "Ryutaro Shirakawa and Sakurako Goto-Ito and Kota Goto and Shonosuke Wakayama and Haremaru Kubo and Natsumi Sakata and Trinh, {Duc Anh} and Atsushi Yamagata and Yusuke Sato and Hiroshi Masumoto and Jinglei Cheng and Toyoshi Fujimoto and Shuya Fukai and Hisanori Horiuchi",
note = "Funding Information: We are grateful to Tomohito Higashi for comments on the manuscript. We thank the beamline staff of BL41XU of SPring‐8 for technical help during data collection. We thank the staff of Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. We also thank Jennifer Lippincott‐Schwartz and Feng Zhang for providing plasmids. This work was supported by JSPS Grants‐in‐Aid for Scientific Research 16K08574 (R.S.), 17K15072 (S.G.‐I.), and 16H05148 (H.H.), JST CREST JPMJCR12M5 (S.F.), and a grant from Takeda Science Foundation (R.S.). Funding Information: We are grateful to Tomohito Higashi for comments on the manuscript. We thank the beamline staff of BL41XU of SPring-8 for technical help during data collection. We thank the staff of Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support. We also thank Jennifer Lippincott-Schwartz and Feng Zhang for providing plasmids. This work was supported by JSPS Grants-in-Aid for Scientific Research 16K08574 (R.S.), 17K15072 (S.G.-I.), and 16H05148 (H.H.), JST CREST JPMJCR12M5 (S.F.), and a grant from Takeda Science Foundation (R.S.). Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = apr,
day = "15",
doi = "10.15252/embj.2019104120",
language = "English",
volume = "39",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "8",
}