ArticleCellular and molecular life sciences : CMLS2021
Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells.The Journal of biological chemistry · 2026Article
- Article
- [Molecular Mechanisms of Intervention With Lishukang Capsule in a Rat Model of High-Altitude Pulmonary Edema].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Golgi retention of KIT in gastrointestinal stromal tumour cells is phospholipase D activity-dependent.Scientific reports · 2025Article
- Lipids in Extracellular Vesicles: What Can Be Learned about Membrane Structure and Function?Cold Spring Harbor perspectives in biology · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have here investigated whether changes in these lipids might be important for regulation of transport to the Golgi using the protein toxin ricin. Modulation of DAG and PA levels using DAG kinase (DGK) and phospholipase D (PLD) inhibitors gave a strong increase in retrograde ricin transport, but had little impact on ricin recycling or degradation. Inhibitor treatment strongly affected the endosome morphology, increasing endosomal tubulation and size. Furthermore, ricin was present in these tubular structures together with proteins known to regulate retrograde transport. Using siRNA to knock down different isoforms of PLD and DGK, we found that several isoforms of PLD and DGK are involved in regulating ricin transport to the Golgi. Finally, by performing lipidomic analysis we found that the DGK inhibitor gave a weak, but expected, increase in DAG levels, while the PLD inhibitor gave a strong and unexpected increase in DAG levels, showing that it is important to perform lipidomic analysis when using inhibitors of lipid metabolism.
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Registered trials
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