Tissue Distribution and Regulation of the Small Sar1b GTPase in Mice

Abstract

Background/Aims: Sar1b GTPase (Sar1b) represents an obligatory component of COPII vesicles that bud from the endoplasmic reticulum to transport proteins to the Golgi apparatus. Its genetic mutations lead to a severe disorder known as chylomicron retention disease. Despite growing knowledge on Sar1b, little is known about it tissue distribution and regulation, which constitute the aims of the present study. We aimed to determine the Sar1b tissue distribution and modulation by a high-fat diet and gene forcing using transgenic mice in comparison to wild-type mice. Methods: The expression pattern of Sar1b was studied in different organs of wild-type and Sar1b transgenic mice by qRT-PCR and Western blot. The effect of transgenesis and insulin resistance induced by a 12-week high-fat diet on Sar1b gene expression was also assessed by qRT-PCR. Results: Evaluation of Sar1b mRNA revealed the skeletal muscle as the tissue with the highest Sar1b expression, followed by the heart and liver, the organs composing the digestive tract, the brain and finally the lung and the adipose tissue. Sar1b protein expression levels follow a similar pattern among the organs, except for its lower expression in the heart. While the high-fat diet did not exert any significant alterations, Sar1b transgenic mice displayed higher gene expression in the liver, ileum, jejunum, proximal and distal colon compared to wild-type mice. Conclusion: Our study supports the importance of Sar1b in organs involved in lipid transport and/or calcium trafficking such as the liver, intestine, skeletal muscle and heart.

Knockdown of SAR1B suppresses proliferation and induces apoptosis of RKO colorectal cancer cells

“…It has been demonstrated that SAR1B GTPase is central to lipid metabolism and regulates chylomicron secretion by the small intestine (27,28). According to previous reports, the expression of SAR1B was identified in cell lines (including Caco-2/15 and McArdle-RH7777 cells), tissues and blood samples from patients (12,29,30). In the present study, SAR1B expression was upregulated in CRC patient samples.…”

Insights from human congenital disorders of intestinal lipid metabolism

“…Evaluation of Sar1b mRNA revealed skeletal muscle as the tissue with the highest Sar1b expression, followed by the heart and liver, the organs composing the digestive tract, the brain, and fi nally the lung and the adipose tissue ( 230 ). Sar1b protein expression levels follow a similar pattern among the organs, except for its higher expression in the heart.…”

Sar1 Affects the Localization of Perilipin 2 to Lipid Droplets

“…Activated Sar1 binds to the ER membrane and recruits the Sec23/24 complex [ 21 ]. There are two isoforms of Sar1, Sar1a and Sar1b, that are similar enough that each can compensate for a deficiency in the other during COPⅡ vesicle budding [ 22 , 23 ]. Although the two isoforms have high sequence homology, there are some functional differences.…”

“…Although the two isoforms have high sequence homology, there are some functional differences. For example, Sar1a exchanges GDP-GTP faster than Sar1b, and the affinity of Sar1b to Sec23 is higher than that of Sar1a [ 22 , 24 ]. SAR1B genetic defects cause chylomicron retention diseases, despite the presence of Sar1a, and they are characterized by a remarkable reduction of plasma TG levels and appearance of intracellular vesicles containing neutral lipids in enterocytes [ 24 , 25 ].…”