SNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network

Archan Chakraborty, Wei Cheng Lin, Yu Tsun Lin, Kuang Jing Huang, Pei Yu Wang, Ian Yi Feng Chang, Hsiang Iu Wang, Kung Ting Ma, Chun Yen Wang, Xuan Rong Huang, Yen Hsien Lee, Bi Chang Chen, Ya Ju Hsieh, Kun Yi Chien, Tzu Yang Lin, Ji Long Liu, Li Ying Sung, Jau Song Yu, Yu Sun Chang, Li Mei Pai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations

Abstract

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5′-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS.APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

Original languageEnglish
Article numberjcs240200
JournalJournal of Cell Science
Volume133
Issue number9
DOIs
StatePublished - 05 2020

Bibliographical note

Publisher Copyright:
© 2020. Published by The Company of Biologists Ltd.

Keywords

  • CTPS filaments
  • Histidine
  • Intermediate filaments
  • SNAP29

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