Expression of Sar1b enhances chylomicron assembly and key components of the coat protein complex II system driving vesicle budding.

Emile Levy, Elodie Harmel, Martine Laville, Rocio Sanchez, Léa Emonnot, Daniel Sinnett, Ehud Ziv, Edgard Delvin, Patrick Couture, Valérie Marcil, Alain T Sane

Research Centre, Mother and Child University Hospital Center, Sainte-Justine, Montreal, Quebec, Canada. emile.levy@recherche-ste-justine.qc.ca

Arteriosclerosis, thrombosis, and vascular biology 2011 Nov

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SAR1b plays a significant role in the assembly, organization, and function of the coat protein complex II, a critical complex for the transport of proteins from the endoplasmic reticulum to the Golgi. Recently, mutations in SARA2 have been associated with lipid absorption disorders. However, functional studies on Sar1b-mediated lipid synthesis pathways and lipoprotein packaging have not been performed. Sar1b was overexpressed in Caco-2/15 cells and resulted in significantly augmented triacylglycerol, cholesteryl ester, and phospholipid esterification and secretion and markedly enhanced chylomicron production. It also stimulated monoacylglycerol acyltransferase/diacylglycerol acyltransferase activity and enhanced apolipoprotein B-48 protein synthesis, as well as elevated microsomal triglyceride transfer protein activity. Along with the enhanced chylomicrons, microsomes were characterized by abundant Sec12, the guanine exchange factor that promotes the localization of Sar1b in the endoplasmic reticulum. Furthermore, coimmunoprecipitation experiments revealed high levels of the complex components Sec23/Sec24 and p125, the Sec23-interacting protein. Finally, a pronounced interaction of Sec23/Sec24 with sterol regulatory element binding protein (SREBP) cleavage-activating protein and SREBP-1c was noted, thereby permitting the transfer of the transcription factor SREBP-1c to the nucleus for the activation of genes involved in lipid metabolism. Our data suggest that Sar1b expression may promote intestinal lipid transport with the involvement of the coat protein complex II network and the processing of SREBP-1c.

Citation

Emile Levy, Elodie Harmel, Martine Laville, Rocio Sanchez, Léa Emonnot, Daniel Sinnett, Ehud Ziv, Edgard Delvin, Patrick Couture, Valérie Marcil, Alain T Sane. Expression of Sar1b enhances chylomicron assembly and key components of the coat protein complex II system driving vesicle budding. Arteriosclerosis, thrombosis, and vascular biology. 2011 Nov;31(11):2692-9