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Signal Transduction and Modulation

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

The novel depalmitoylating enzyme family regulates bi-directional trafficking of HRas between the Golgi apparatus and the plasma membrane

  • P2-056
  • 村上 達郎 / Tatsuro Murakami:1,2,3 関谷 敦志 / Atsushi Sekiya:1,2,3 深田 優子 / Yuko Fukata:1,2 深田 正紀 / Masaki Fukata:1,2 
  • 1:自然科学研究機構・生理研・細胞器官系・生体膜 / Div Membrane Physiol, Dept Cell Physiol, National Institute for Physiological Sciences (NIPS) 2:総合研究大学院大学・生命科学研究科・生理科学専攻 / Dept Physiol Science, School of Life Science, The Graduate Univ for Advanced Studies [SOKENDAI] 3:日本学術振興会特別研究員 / JSPS Research Fellow 

Palmitoylation, a unique reversible post-translational lipid modification, adds the palmitate to proteins on specific cystein residues and regulates protein trafficking and functions. We identified the DHHC palmitoylating enzyme family in 2004 and have obtained important insights into various cellular functions since then. However, the significance of palmitoyl cycles remains incompletely understood because authentic depalmitoylating enzymes have been unidentified over 35 years. Here, to identify depalmitoylating enzymes, we focused on the uncharacterized serine hydrolase family including protease, lipase, esterase and thioesterase because depalmitoylating enzymes belong to thioesterase and classical depalmitoylating enzyme candidates, APT1 (Lypla1), APT2 and PPT1, belong to serine hydrolase family. We isolated 38 unannotated serine hydrolase genes and examined their enzymatic activities by metabolic labeling of HRas with tritium-palmitate. We found that six candidate proteins robustly reduced palmitoylation levels of HRas. Further analysis revealed their substrate specificities toward representative palmitoylated substrates, GAP-43, Fyn, Lck, SNAP-25, Paralemmin, NCAM140 and PSD-95. Intriguingly, when we examined the localization of these six candidates, they differently localized at the plasma membrane, ER or cytosol. Using fluorescence recovery after photobleaching analysis and photoactivation method, we propose that individual depalmitoylating enzyme could regulate different steps of HRas trafficking acting on specific palmitoylated cysteine sites at different subcellular locations.

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