PUBLICATION
A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience
- Authors
- Wang, C., Wang, B., Pandey, T., Long, Y., Zhang, J., Oh, F., Sima, J., Guo, R., Liu, Y., Zhang, C., Mukherjee, S., Bassik, M., Lin, W., Deng, H., Vale, G., McDonald, J.G., Shen, K., Ma, D.K.
- ID
- ZDB-PUB-221115-68
- Date
- 2022
- Source
- Nature communications 13: 6805 (Journal)
- Registered Authors
- Long, Yong
- Keywords
- none
- MeSH Terms
-
- Animals
- Caenorhabditis elegans*/genetics
- Caenorhabditis elegans*/metabolism
- Cell Membrane/metabolism
- Endoplasmic Reticulum/metabolism
- Humans
- Mammals/metabolism
- Phospholipids/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 36357390 Full text @ Nat. Commun.
Citation
Wang, C., Wang, B., Pandey, T., Long, Y., Zhang, J., Oh, F., Sima, J., Guo, R., Liu, Y., Zhang, C., Mukherjee, S., Bassik, M., Lin, W., Deng, H., Vale, G., McDonald, J.G., Shen, K., Ma, D.K. (2022) A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience. Nature communications. 13:6805.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping