Open AccessSNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network
Author(s) -
Archan Chakraborty,
Wen-Yinn Lin,
Yung Hsiang Lin,
Kuang-Jing Huang,
Peiyu Wang,
Ian YiFeng Chang,
Kung-Ting Ma,
Chun-Yen Wang,
Xuan-Rong Huang,
YenHsien Lee,
Bi-Chang Chen,
Ya-Ju Hsieh,
Kun-Yi Chien,
Tzu-Yang Lin,
JiLong Liu,
Li-Ying Sung,
JauSong Yu,
YuSun Chang,
LiMei Pai
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.240200
Subject(s) - biology , histidine , cytokeratin , atp synthase , microbiology and biotechnology , biochemistry , enzyme , immunology , immunohistochemistry
Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5′-triphosphate synthase (CTPS), 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 Gln 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 SNAP29 regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of synaptosome-associated protein 29 (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.