Trans-Golgi Proteins Participate in the Control of Lipid Droplet and Chylomicron Formation

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2012 Oct 5

PMID 23033902

Citations 17

Authors

Deike Hesse

Alexander Jaschke

Bomee Chung

Annette Schurmann

Affiliations

Soon will be listed here.

Abstract

LDs (lipid droplets) carrying TAG (triacylglycerol) and cholesteryl esters are emerging as dynamic cellular organelles that are generated in nearly every cell. They play a key role in lipid and membrane homoeostasis. Abnormal LD dynamics are associated with the pathophysiology of many metabolic diseases, such as obesity, diabetes, atherosclerosis, fatty liver and even cancer. Chylomicrons, stable droplets also consisting of TAG and cholesterol are generated in the intestinal epithelium to transport exogenous (dietary) lipids after meals from the small intestine to tissues for degradation. Defective chylomicron formation is responsible for inherited lipoprotein deficiencies, including abetalipoproteinaemia, hypobetalipoproteinaemia and chylomicron retention disease. These are disorders sharing characteristics such as fat malabsorption, low levels of circulating lipids and fat-soluble vitamins, failure to thrive in early childhood, ataxic neuropathy and visual impairment. Thus understanding the molecular mechanisms governing the dynamics of LDs and chylomicrons, namely, their biogenesis, growth, maintenance and degradation, will not only clarify their molecular role, but might also provide additional indications to treatment of metabolic diseases. In this review, we highlight the role of two small GTPases [ARFRP1 (ADP-ribosylation factor related protein 1) and ARL1 (ADP-ribosylation factor-like 1)] and their downstream targets acting on the trans-Golgi (Golgins and Rab proteins) on LD and chylomicron formation.

Citing Articles

Relevance of Lipoprotein Composition in Endothelial Dysfunction and the Development of Hypertension.

Ramirez-Melo L, Estrada-Luna D, Rubio-Ruiz M, Castaneda-Ovando A, Fernandez-Martinez E, Jimenez-Osorio A Int J Mol Sci. 2025; 26(3).

PMID: 39940892 PMC: 11817739. DOI: 10.3390/ijms26031125.

Rab30 facilitates lipid homeostasis during fasting.

Smith D, Liu B, Wolfgang M Nat Commun. 2024; 15(1):4469.

PMID: 38796472 PMC: 11127972. DOI: 10.1038/s41467-024-48959-x.

TANGO6 regulates cell proliferation via COPI vesicle-mediated RPB2 nuclear entry.

Feng Z, Liu S, Su M, Song C, Lin C, Zhao F Nat Commun. 2024; 15(1):2371.

PMID: 38490996 PMC: 10943085. DOI: 10.1038/s41467-024-46720-y.

Effect of modification of polystyrene nanoparticles with different bile acids on their oral transport.

Deng F, Bae Y Nanomedicine. 2022; 48:102629.

PMID: 36410698 PMC: 9918699. DOI: 10.1016/j.nano.2022.102629.

Sus_circPAPPA2 Regulates Fat Deposition in Castrated Pigs through the miR-2366/ Pathway.

Liu X, Bai Y, Cui R, He S, Zhao X, Wu K Biomolecules. 2022; 12(6).

PMID: 35740877 PMC: 9220968. DOI: 10.3390/biom12060753.

References

Starr T, Sun Y, Wilkins N, Storrie B . Rab33b and Rab6 are functionally overlapping regulators of Golgi homeostasis and trafficking. Traffic. 2010; 11(5):626-36. DOI: 10.1111/j.1600-0854.2010.01051.x. View

Zahn C, Hommel A, Lu L, Hong W, Walther D, Florian S . Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells. Mol Membr Biol. 2006; 23(6):475-85. DOI: 10.1080/09687860600840100. View

Derby M, Gleeson P . New insights into membrane trafficking and protein sorting. Int Rev Cytol. 2007; 261:47-116. DOI: 10.1016/S0074-7696(07)61002-X. View

Kuerschner L, Moessinger C, Thiele C . Imaging of lipid biosynthesis: how a neutral lipid enters lipid droplets. Traffic. 2007; 9(3):338-52. DOI: 10.1111/j.1600-0854.2007.00689.x. View

Lu L, Tai G, Hong W . Interaction of Arl1 GTPase with the GRIP domain of Golgin-245 as assessed by GST (glutathione-S-transferase) pull-down experiments. Methods Enzymol. 2006; 404:432-41. DOI: 10.1016/S0076-6879(05)04038-3. View

Horiguchi Y, Araki M, Motojima K . Identification and characterization of the ER/lipid droplet-targeting sequence in 17beta-hydroxysteroid dehydrogenase type 11. Arch Biochem Biophys. 2008; 479(2):121-30. DOI: 10.1016/j.abb.2008.08.020. View

Lu X, Copeland N, Gilbert D, Jenkins N, Londos C, Kimmel A . The murine perilipin gene: the lipid droplet-associated perilipins derive from tissue-specific, mRNA splice variants and define a gene family of ancient origin. Mamm Genome. 2001; 12(9):741-9. DOI: 10.1007/s00335-01-2055-5. View

Levy E, Stan S, Delvin E, Menard D, Shoulders C, Garofalo C . Localization of microsomal triglyceride transfer protein in the Golgi: possible role in the assembly of chylomicrons. J Biol Chem. 2002; 277(19):16470-7. DOI: 10.1074/jbc.M102385200. View

Setty S, Shin M, Yoshino A, Marks M, Burd C . Golgi recruitment of GRIP domain proteins by Arf-like GTPase 1 is regulated by Arf-like GTPase 3. Curr Biol. 2003; 13(5):401-4. DOI: 10.1016/s0960-9822(03)00089-7. View

10.

Derby M, Lieu Z, Brown D, Stow J, Goud B, Gleeson P . The trans-Golgi network golgin, GCC185, is required for endosome-to-Golgi transport and maintenance of Golgi structure. Traffic. 2007; 8(6):758-73. DOI: 10.1111/j.1600-0854.2007.00563.x. View

11.

Swift L, Zhu M, Kakkad B, Jovanovska A, Neely M, Valyi-Nagy K . Subcellular localization of microsomal triglyceride transfer protein. J Lipid Res. 2003; 44(10):1841-9. DOI: 10.1194/jlr.M300276-JLR200. View

12.

Rejman Lipinski A, Heymann J, Meissner C, Karlas A, Brinkmann V, Meyer T . Rab6 and Rab11 regulate Chlamydia trachomatis development and golgin-84-dependent Golgi fragmentation. PLoS Pathog. 2009; 5(10):e1000615. PMC: 2752117. DOI: 10.1371/journal.ppat.1000615. View

13.

Sinka R, Gillingham A, Kondylis V, Munro S . Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins. J Cell Biol. 2008; 183(4):607-15. PMC: 2582897. DOI: 10.1083/jcb.200808018. View

14.

Gillingham A, Munro S . Long coiled-coil proteins and membrane traffic. Biochim Biophys Acta. 2003; 1641(2-3):71-85. DOI: 10.1016/s0167-4889(03)00088-0. View

15.

Sannerud R, Saraste J, Goud B . Retrograde traffic in the biosynthetic-secretory route: pathways and machinery. Curr Opin Cell Biol. 2003; 15(4):438-45. DOI: 10.1016/s0955-0674(03)00077-2. View

16.

Wu C, Howell K, Neville M, Yates 3rd J, McManaman J . Proteomics reveal a link between the endoplasmic reticulum and lipid secretory mechanisms in mammary epithelial cells. Electrophoresis. 2000; 21(16):3470-82. DOI: 10.1002/1522-2683(20001001)21:16<3470::AID-ELPS3470>3.0.CO;2-G. View

17.

Levy E . The genetic basis of primary disorders of intestinal fat transport. Clin Invest Med. 1996; 19(5):317-24. View

18.

Subramani D, Alahari S . Integrin-mediated function of Rab GTPases in cancer progression. Mol Cancer. 2010; 9:312. PMC: 3003658. DOI: 10.1186/1476-4598-9-312. View

19.

Iqbal J, Hussain M . Intestinal lipid absorption. Am J Physiol Endocrinol Metab. 2009; 296(6):E1183-94. PMC: 2692399. DOI: 10.1152/ajpendo.90899.2008. View

20.

Guo Y, Walther T, Rao M, Stuurman N, Goshima G, Terayama K . Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature. 2008; 453(7195):657-61. PMC: 2734507. DOI: 10.1038/nature06928. View