المؤلفون: Jiang, Wei, De Belly, Henry, Wang, Bingying, Wong, Andrew, Kim, Minseo, Oh, Fiona, DeGeorge, Jason, Huang, Xinya, Guang, Shouhong, Weiner, Orion, Ma, Dengke

المصدر: Science Advances. 10(4)

مصطلحات موضوعية: Adult, Humans, Animals, Longevity, Thrombospondin 1, Adverse Childhood Experiences, Caenorhabditis elegans, Resilience, Psychological, Tetraspanins, Transcription Factors, Caenorhabditis elegans Proteins, Histone Acetyltransferases

الوصف: Early-life stress experiences can produce lasting impacts on organismal adaptation and fitness. How transient stress elicits memory-like physiological effects is largely unknown. Here, we show that early-life thermal stress strongly up-regulates tsp-1, a gene encoding the conserved transmembrane tetraspanin in C. elegans. TSP-1 forms prominent multimers and stable web-like structures critical for membrane barrier functions in adults and during aging. Increased TSP-1 abundance persists even after transient early-life heat stress. Such regulation requires CBP-1, a histone acetyltransferase that facilitates initial tsp-1 transcription. Tetraspanin webs form regular membrane structures and mediate resilience-promoting effects of early-life thermal stress. Gain-of-function TSP-1 confers marked C. elegans longevity extension and thermal resilience in human cells. Together, our results reveal a cellular mechanism by which early-life thermal stress produces long-lasting memory-like impact on organismal resilience and longevity.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5fw4s85pTest

المؤلفون: Wang, Changnan, Wang, Bingying, Pandey, Taruna, Long, Yong, Zhang, Jianxiu, Oh, Fiona, Sima, Jessica, Guo, Ruyin, Liu, Yun, Zhang, Chao, Mukherjee, Shaeri, Bassik, Michael, Lin, Weichun, Deng, Huichao, Vale, Goncalo, McDonald, Jeffrey G, Shen, Kang, Ma, Dengke K

المصدر: Nature communications. 13(1)

مصطلحات موضوعية: Cell Membrane, Endoplasmic Reticulum, Animals, Zebrafish, Mammals, Humans, Caenorhabditis elegans, Phospholipids, Genetics, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance

الوصف: Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through conserved homeostatic mechanisms. Here we report an exceptionally large and evolutionarily conserved protein LPD-3 in C. elegans that mediates lipid trafficking to confer cold resilience. We identify lpd-3 mutants in a mutagenesis screen for genetic suppressors of the lipid desaturase FAT-7. LPD-3 bridges the endoplasmic reticulum (ER) and plasma membranes (PM), forming a structurally predicted hydrophobic tunnel for lipid trafficking. lpd-3 mutants exhibit abnormal phospholipid distribution, diminished FAT-7 abundance, organismic vulnerability to cold, and are rescued by Lecithin comprising unsaturated phospholipids. Deficient lpd-3 homologues in Zebrafish and mammalian cells cause defects similar to those observed in C. elegans. As mutations in BLTP1, the human orthologue of lpd-3, cause Alkuraya-Kucinskas syndrome, LPD-3 family proteins may serve as evolutionarily conserved highway bridges critical for ER-associated non-vesicular lipid trafficking and resilience to cold stress in eukaryotic cells.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1fj2h27hTest