A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience.
Changnan WangBingying WangTaruna PandeyYong LongJianxiu ZhangFiona OhJessica SimaRuyin GuoYun LiuChao ZhangShaeri MukherjeeMichael C BassikWeichun LinHuichao DengGonçalo ValeJeffrey G McDonaldKang ShenDengke K MaPublished in: Nature communications (2022)
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.
Keyphrases
- fatty acid
- endoplasmic reticulum
- induced apoptosis
- climate change
- transcription factor
- cell cycle arrest
- social support
- adipose tissue
- endothelial cells
- depressive symptoms
- endoplasmic reticulum stress
- estrogen receptor
- crispr cas
- oxidative stress
- cell death
- particulate matter
- dna methylation
- heat stress
- risk assessment
- breast cancer cells
- small molecule
- copy number
- case report
- induced pluripotent stem cells
- anaerobic digestion