RT Journal Article
SR Electronic
T1 Pla2g12b is Essential for Expansion of Nascent Lipoprotein Particles
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.02.502564
DO 10.1101/2022.08.02.502564
A1 James H. Thierer
A1 Ombretta Foresti
A1 Pradeep Kumar Yadav
A1 Meredith H. Wilson
A1 Tabea Moll
A1 Meng-Chieh Shen
A1 Elisabeth M. Busch-Nentwich
A1 Margaret Morash
A1 Karen L. Mohlke
A1 John F. Rawls
A1 Vivek Malhotra
A1 M. Mahmood Hussain
A1 Steven A. Farber
YR 2022
UL http://biorxiv.org/content/early/2022/08/03/2022.08.02.502564.abstract
AB SUMMARY Triglyceride-rich lipoproteins (TRLs) are micelle-like particles that enable efficient transport of lipids throughout the bloodstream, but also promote atherosclerotic cardiovascular disease. Despite this central relevance to cardiovascular disease, very little is known about how lipids are loaded onto nascent TRLs prior to secretion. Here we show that Pla2g12b, a gene with no previously described function, concentrates components of the TRL biogenesis machinery along the ER membrane to ensure efficient delivery of lipids to nascent TRLs. We find that the lipid-poor TRLs secreted in PLA2G12B-/- mice and zebrafish support surprisingly normal growth and physiology while conferring profound resistance to atherosclerosis, and demonstrate that these same processes are conserved in human cells. Together these findings shed new light on the poorly understood process of TRL expansion, ascribe function to the previously uncharacterized gene Pla2g12b, and reveal a promising new strategy to remodel serum lipoproteins to prevent cardiovascular disease.Competing Interest StatementThe authors have declared no competing interest.