A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience

Changnan Wang, Bingying Wang, Taruna Pandey, Yong Long, Jianxiu Zhang, Fiona Oh, Jessica Sima, Ruyin Guo, Yun Liu, Chao Zhang, Shaeri Mukherjee, Michael Bassik, Weichun Lin, Huichao Deng, Goncalo Vale, Jeffrey G. McDonald, Kang Shen and Dengke K. Ma ()
Additional contact information
Changnan Wang: University of California San Francisco
Bingying Wang: University of California San Francisco
Taruna Pandey: University of California San Francisco
Yong Long: Chinese Academy of Sciences
Jianxiu Zhang: Stanford University
Fiona Oh: University of California San Francisco
Jessica Sima: University of California San Francisco
Ruyin Guo: University of California San Francisco
Yun Liu: University of Texas Southwestern Medical Center
Chao Zhang: Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Shaeri Mukherjee: University of California, San Francisco
Michael Bassik: Stanford University School of Medicine
Weichun Lin: University of Texas Southwestern Medical Center
Huichao Deng: Howard Hughes Medical Institute, Stanford University
Goncalo Vale: University of Texas Southwestern Medical Center
Jeffrey G. McDonald: University of Texas Southwestern Medical Center
Kang Shen: Howard Hughes Medical Institute, Stanford University
Dengke K. Ma: University of California San Francisco

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34450-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34450-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34450-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().