Possible Involvement of Heterotrimeric G Proteins in the Organization of the Golgi Apparatus

Yamaguchi, Tomohiro; Yamamoto, Akira; Furuno, Akiko; Hatsuzawa, Kiyotaka; Tani, Kazuhide; Himeno, Masaru; Tagaya, Mitsuo

doi:10.1074/jbc.272.40.25260

Cited by 38 publications

(47 citation statements)

References 55 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: 77%

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: 77%

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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“…The action mechanism of BFA is known as the inhibition of the Golgi membrane-catalyzed GDP/GTP exchange of ARF, which results in the lack of formation of transport vesicles (Lippincott-Schwartz et al, 1990;Donaldson et al, 1992). The relevant molecular targets of NDGA are presently unknown, but recent work has implicated heterotrimeric G proteins in the NDGA-mediated disruption of Golgi morphology (Yamaguchi et al, 1997). In addition, NDGA is a phospholipase A 2 and lipoxygenase inhibitor, which suggests a possible role for eicosanoids in regulating membrane trafficking (Tagaya et al, 1993).…”

Section: Figmentioning

confidence: 99%

Effect of Nordihydroguaiaretic Acid on the Secretion of Lipoprotein Lipase

Kim

Park²,

Park³

2002

BMB Reports

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Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, inhibits the secretion of proteins and causes the redistribution of resident Golgi proteins into the endoplasmic reticulum (ER). In this study, the effect of NDGA on lipoprotein lipase (LPL) secretion was investigated in 3T3-L1 adipocytes, and compared with those of brefeldin A (BFA), a well-known fungal metabolite that exhibits similar ER-Golgi redistribution. Both BFA and NDGA blocked secretions of LPL. In the presence of BFA, the active and dimeric LPL was accumulated in adipocytes. After endoglycosidase H (endo H) digestion, the proportion of LPL subunits with partially endo Hsensitive oligosaccharide was significantly increased with BFA. However, in the presence of NDGA, the cellular LPL became inactive, and only the endo H-sensitive fraction of the LPL subunit was observed. An increase of the aggregated forms was observed in the fractions of the sucrose-density gradient ultracentrifugation. These properties of LPL in the NDGA-treated cells were similar to those of LPL that is retained in ER, and the effects of NDGA could not be reversed by BFA. These results indicate that the inhibitory mechanism of NDGA on the LPL secretion is functionally different from the ER-Golgi redistribution that is induced by BFA.

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“…In addition to caveolin, heterotrimeric G proteins have been localized to the Golgi complex, and several lines of evidence support a role in intracellular protein transport (Bomsel and Mostov, 1992;Helms, 1995). More recently, heterotrimeric G proteins have been implicated in the regulation of Golgi structure (Jamora et al, 1997;Yamaguchi et al, 1997). We previously showed that a putative heterotrimeric G protein inhibits the fusion of COPI-coated vesicles at early stages of the Golgi complex and found that Golgilocalized G proteins reside in a detergent-insoluble complex (Helms et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Sphingomyelin-enriched Microdomains at the Golgi Complex

Gkantiragas

Brügger

Stüven

et al. 2001

MBoC

155

134

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Sphingomyelin- and cholesterol-enriched microdomains can be isolated as detergent-resistant membranes from total cell extracts (total-DRM). It is generally believed that this total-DRM represents microdomains of the plasma membrane. Here we describe the purification and detailed characterization of microdomains from Golgi membranes. These Golgi-derived detergent-insoluble complexes (GICs) have a low buoyant density and are highly enriched in lipids, containing 25% of total Golgi phospholipids including 67% of Golgi-derived sphingomyelin, and 43% of Golgi-derived cholesterol. In contrast to total-DRM, GICs contain only 10 major proteins, present in nearly stoichiometric amounts, including the α- and β-subunits of heterotrimeric G proteins, flotillin-1, caveolin, and subunits of the vacuolar ATPase. Morphological data show a brefeldin A-sensitive and temperature-sensitive localization to the Golgi complex. Strikingly, the stability of GICs does not depend on its membrane environment, because, after addition of brefeldin A to cells, GICs can be isolated from a fused Golgi-endoplasmic reticulum organelle. This indicates that GIC microdomains are not in a dynamic equilibrium with neighboring membrane proteins and lipids. After disruption of the microdomains by cholesterol extraction with cyclodextrin, a subcomplex of several GIC proteins including the B-subunit of the vacuolar ATPase, flotillin-1, caveolin, and p17 could still be isolated by immunoprecipitation. This indicates that several of the identified GIC proteins localize to the same microdomains and that the microdomain scaffold is not required for protein interactions between these GIC proteins but instead might modulate their affinity.

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Possible Involvement of Heterotrimeric G Proteins in the Organization of the Golgi Apparatus

Cited by 38 publications

References 55 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

Effect of Nordihydroguaiaretic Acid on the Secretion of Lipoprotein Lipase

Sphingomyelin-enriched Microdomains at the Golgi Complex

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