Regulation of Golgi Structure through Heterotrimeric G Proteins

Takizawa, Peter A.; Zaarour, Rania F.; Denesvre, Caroline; Faulkner, D. John; Malhotra, Vivek

doi:10.1016/s0092-8674(00)80449-3

Cited by 112 publications

(94 citation statements)

References 40 publications

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“…Because the morphology of the Golgi is changed upon cholesterol treatment of the cells, these data implicate a function for heterotrimeric G proteins in the maintenance of the Golgi structure as well. This is supported by previous findings showing that possibly free G␤␥ subunits are involved in maintenance of the Golgi structure (74,75). Although the mechanism of G protein-mediated signaling cascades at the Golgi complex is not well understood, our data now suggest that these cascades could be regulated by lipid-enriched microdomains, similar to many other signaling events at the plasma membrane (16).…”

Section: Discussionsupporting

confidence: 91%

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Stüven

Porat

Shimron

et al. 2003

Journal of Biological Chemistry

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Transport of proteins between intracellular membrane compartments is mediated by a protein machinery that regulates the budding and fusion processes of individual transport steps. Although the core proteins of both processes are defined at great detail, much less is known about the involvement of lipids. Here we report that changing the cellular balance of cholesterol resulted in changes of the morphology of the Golgi apparatus, accompanied by an inhibition of protein transport. By using a well characterized cell-free intra-Golgi transport assay, these observations were further investigated, and it was found that the transport reaction is sensitive to small changes in the cholesterol content of Golgi membranes. Addition as well as removal of cholesterol (10 ؎ 6%) to Golgi membranes by use of methyl-␤-cyclodextrin specifically inhibited the intra-Golgi transport assay. Transport inhibition occurred at the fusion step. Modulation of the cholesterol content changed the lipid raft partitioning of phosphatidylcholine and heterotrimeric G proteins, but not of other (non) lipid raft proteins and lipids. We suggest that the cholesterol balance in Golgi membranes plays an essential role in intra-Golgi protein transport and needs to be carefully regulated to maintain the structural and functional organization of the Golgi apparatus.

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Section: Discussionsupporting

confidence: 91%

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Stüven

Porat

Shimron

et al. 2003

Journal of Biological Chemistry

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“…Gilman and colleagues 36 have shown that sequestration of heterotrimeric G protein bg subunits in intact cells strongly inhibits clathrin-coated pit-mediated endocytosis and causes rearrangement of the actin cytoskeleton, and concluded that free bg subunits of G proteins function to permit endocytosis on activation of G protein-coupled receptors. Another line of evidence suggesting the importance of bg subunits of G proteins in vesiculation was shown by Malhotra and colleagues 37,38 . They have shown that ilimaquinone, a marine sponge metabolite, causes complete vesiculation of the Golgi stacks, and later concluded using an elegantly designed reconstitution assay that ilimaquinone-mediated Golgi vesiculation occurs through activation of heterotrimeric G proteins and that it is the free bg subunits and not the activated a subunit that triggers Golgi vesiculation.…”

Section: Discussionmentioning

confidence: 89%

“…All S1P receptors (type [1][2][3][4][5] are classified into a family of G proteincoupled receptors and show distinct expression in tissues and cells, and also show unique G protein-coupling patterns, suggesting distinctive functions 34 . We reasoned that S1P signalling might be involved in the exosomal MVE maturation, because the subunits of G proteins are known to be involved in various types of fission/ fusion events in vesicular trafficking [35][36][37] and protein sorting 38 . In the present studies, we have found that inhibitory G protein (Gi)-coupled S1P receptors on MVEs undergo continuous activation through a constant supply of S1P within the organelles.…”

mentioning

confidence: 99%

Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes

et al. 2013

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During late endosome maturation, cargo molecules are sorted into intralumenal vesicles (ILVs) of multivesicular endosomes (MVEs), and are either delivered to lysosomes for degradation or fused with the plasma membranes for exosome release. The mechanism underlying formation of exosomal ILVs and cargo sorting into ILVs destined for exosome release is still unclear. Here we show that inhibitory G protein (Gi)-coupled sphingosine 1-phosphate (S1P) receptors regulate exosomal MVE maturation. Gi-coupled S1P receptors on MVEs are constitutively activated through a constant supply of S1P via autocrine activation within organelles. We also found that the continuous activation of Gi-coupled S1P receptors on MVEs is essential for cargo sorting into ILVs destined for exosome release. Our results reveal a mechanism underlying ESCRT-independent maturation of exosomal MVEs.

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“…It has been suggested previously that IQ is able to activate one or more heterotrimeric G-proteins located on the Golgi (25). The activated G-protein dissociates into G␣ and G␤␥ subunits, where the latter remains membrane-associated and causes the fragmentation of the Golgi through downstream mediators.…”

Section: Discussionmentioning

confidence: 99%

Requirement of Phospholipase D for Ilimaquinone-induced Golgi Membrane Fragmentation

Sonoda

Okada

Jahangeer

et al. 2007

Journal of Biological Chemistry

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Although organelles such as the endoplasmic reticulum and Golgi apparatus are highly compartmentalized, these organelles are interconnected through a network of vesicular trafficking. The marine sponge metabolite ilimaquinone (IQ) is known to induce Golgi membrane fragmentation and is widely used to study the mechanism of vesicular trafficking. Although IQ treatment causes protein kinase D (PKD) activation, the detailed mechanism of IQ-induced Golgi membrane fragmentation remains unclear. In this work, we found that IQ treatment of cells caused a robust activation of phospholipase D (PLD). In the presence of 1-butanol but not 2-butanol, IQ-induced Golgi membrane fragmentation was completely blocked. In addition, IQ failed to induce Golgi membrane fragmentation in PLD knock-out DT40 cells. Furthermore, IQ-induced PKD activation was completely blocked by treatment with either 1-butanol or propranolol. Notably, IQ-induced Golgi membrane fragmentation was also blocked by propranolol treatment. These results indicate that PLD-catalyzed formation of phosphatidic acid is a prerequisite for IQ-induced Golgi membrane fragmentation and that enzymatic conversion of phosphatidic acid to diacylglycerol is necessary for subsequent activation of PKD and IQ-induced Golgi membrane fragmentation.Regulated vesicular trafficking is essential for the transport of proteins and lipids between subcellular compartments and for the maintenance of organelles in eukaryotic cells. These organelles help the cell establish an ordered structure within which its complex biochemical reactions and signaling processes are executed. The molecular mechanism underlying vesicular trafficking from the endoplasmic reticulum (ER) 2 to the cell surface through the Golgi apparatus has been investigated extensively. Malhotra and coworkers (1) have reported that the marine sponge metabolite ilimaquinone (IQ) inhibits protein trafficking events by reversibly breaking the Golgi apparatus into small vesicles. Several attempts were made to identify downstream molecules necessary for IQ-induced Golgi membrane vesiculation. Using a reconstitution assay system, protein kinase D (PKD) was identified as a key enzyme responsible for IQinduced Golgi membrane vesiculation (2). However, the exact mechanism underlying IQ-induced Golgi apparatus breakdown, especially a relationship between PKD and lipid remodeling, remains unclear. Membrane trafficking is energetically unfavorable and does not occur spontaneously in vivo, but occurs under strict control of specialized proteins. Evidence is accumulating that these proteins do not act alone but in concert with particular membrane lipids such as phosphoinositides (3), diacylglycerol (DAG) (4), and phosphatidic acid (PA) (5-7). Phospholipases hydrolyze phospholipids, the backbone of biological membranes. Phospholipase activity not only has a profound impact on the structure and stability of cellular membranes but also plays a pivotal role in regulating many critical cellular functions. Phospholipase D (PLD) generates PA, a mul...

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Regulation of Golgi Structure through Heterotrimeric G Proteins

Cited by 112 publications

References 40 publications

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes

Requirement of Phospholipase D for Ilimaquinone-induced Golgi Membrane Fragmentation

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