Pla2g12b drives expansion of triglyceride-rich lipoproteins
© 2024. The Author(s)..
Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins. This activity promotes efficient lipid secretion while preventing excess accumulation of intracellular lipids. We characterize the functional domains, subcellular localization, and interacting partners of PLA2G12B, demonstrating that PLA2G12B is calcium-dependent and tightly associated with the membrane of the endoplasmic reticulum. We also detect profound resistance to atherosclerosis in PLA2G12B mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. Here we identify PLA2G12B as a key driver of triglyceride incorporation into vertebrate lipoproteins.
| Errataetall: |
ErratumIn: Nat Commun. 2024 Mar 22;15(1):2572. - PMID 38519494 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 07. März, Seite 2095 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Thierer, James H [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 3.1.1.4 |
|---|
| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 25.03.2024 published: Electronic ErratumIn: Nat Commun. 2024 Mar 22;15(1):2572. - PMID 38519494 Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-024-46102-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36943658X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36943658X | ||
| 003 | DE-627 | ||
| 005 | 20240325235122.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240308s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-46102-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1346.xml |
| 035 | |a (DE-627)NLM36943658X | ||
| 035 | |a (NLM)38453914 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Thierer, James H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pla2g12b drives expansion of triglyceride-rich lipoproteins |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.03.2024 | ||
| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ErratumIn: Nat Commun. 2024 Mar 22;15(1):2572. - PMID 38519494 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins. This activity promotes efficient lipid secretion while preventing excess accumulation of intracellular lipids. We characterize the functional domains, subcellular localization, and interacting partners of PLA2G12B, demonstrating that PLA2G12B is calcium-dependent and tightly associated with the membrane of the endoplasmic reticulum. We also detect profound resistance to atherosclerosis in PLA2G12B mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. Here we identify PLA2G12B as a key driver of triglyceride incorporation into vertebrate lipoproteins | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Lipoproteins |2 NLM | |
| 650 | 7 | |a Triglycerides |2 NLM | |
| 650 | 7 | |a PLA2G12B protein, mouse |2 NLM | |
| 650 | 7 | |a EC 3.1.1.4 |2 NLM | |
| 700 | 1 | |a Foresti, Ombretta |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Pradeep Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Meredith H |e verfasserin |4 aut | |
| 700 | 1 | |a Moll, Tabea O C |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Meng-Chieh |e verfasserin |4 aut | |
| 700 | 1 | |a Busch-Nentwich, Elisabeth M |e verfasserin |4 aut | |
| 700 | 1 | |a Morash, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Mohlke, Karen L |e verfasserin |4 aut | |
| 700 | 1 | |a Rawls, John F |e verfasserin |4 aut | |
| 700 | 1 | |a Malhotra, Vivek |e verfasserin |4 aut | |
| 700 | 1 | |a Hussain, M Mahmood |e verfasserin |4 aut | |
| 700 | 1 | |a Farber, Steven A |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 07. März, Seite 2095 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:07 |g month:03 |g pages:2095 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-46102-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 07 |c 03 |h 2095 | ||