Caveolin-2 Localizes to the Golgi Complex but Redistributes to Plasma Membrane, Caveolae, and Rafts when Co-expressed with Caveolin-1

Mora, Rosalia; Bonilha, Vera L.; Marmorstein, Alan D.; Scherer, Philipp E.; Brown, Dennis; Lisanti, Michael P.; Rodríguez-Boulan, Enrique

doi:10.1074/jbc.274.36.25708

Cited by 195 publications

(227 citation statements)

References 32 publications

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“…38 As it has been described that NDPK-B is required for the formation of the COPII complex, 74 the recognition of the Cav-8S oligomers at the ER exit sites is likely hampered by NDPK-B deficiency and thus delayed. In accordance with data from recognitiondeficient mutants of Cavs, 64,65 Cavs therefore accumulate in lipid bodies and similar structures. In addition, the phenotype of an acute knockdown of NDPK-B in the zebrafish as well as in cellular models can be explained by hampered caveolae formation.…”

Section: Ndpk-b/nme2 Influences Signal Complex Assembly At the Plasmasupporting

confidence: 68%

“…The Cav-8S oligomers translocate to the ER exit sites where a coat protein complex II (COPII)-dependent export to the Golgi apparatus occurs. [62][63][64] If the recognition of Cavs by COPII is hampered, for example, because of mutations in the recognition sites in Cav1 (or Cav3), the export is delayed leading to accumulation in structures near the ER, eg, lipid bodies. 65 In the Golgi, the Cav-8S further oligomerizes.…”

Section: Ndpk-b/nme2 Influences Signal Complex Assembly At the Plasmamentioning

confidence: 99%

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Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update

Abu-Taha

Heijman

Feng

et al. 2018

Laboratory Investigation

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Heterotrimeric G proteins are pivotal mediators of cellular signal transduction in eukaryotic cells and abnormal G-protein signaling plays an important role in numerous diseases. During the last two decades it has become evident that the activation status of heterotrimeric G proteins is both highly localized and strongly regulated by a number of factors, including a receptor-independent activation pathway of heterotrimeric G proteins that does not involve the classical GDP/GTP exchange and relies on nucleoside diphosphate kinases (NDPKs). NDPKs are NTP/NDP transphosphorylases encoded by the nme/nm23 genes that are involved in a variety of cellular events such as proliferation, migration, and apoptosis. They therefore contribute, for example, to tumor metastasis, angiogenesis, retinopathy, and heart failure. Interestingly, NDPKs are translocated and/or upregulated in human heart failure. Here we describe recent advances in the current understanding of NDPK functions and how they have an impact on local regulation of G-protein signaling.

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Section: Ndpk-b/nme2 Influences Signal Complex Assembly At the Plasmasupporting

confidence: 68%

Section: Ndpk-b/nme2 Influences Signal Complex Assembly At the Plasmamentioning

confidence: 99%

Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update

Abu-Taha

Heijman

Feng

et al. 2018

Laboratory Investigation

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“…Caveolin-1 and -2 are typically expressed in the same cells (most epithelia and endothelia) and caveolin-2 increases the number of ''deep'' caveolae in cells that have caveolin-1. Moreover, caveolin-1 is required for the trafficking of caveolin-2 from the Golgi to the plasma membrane and incorporation of caveolin-2 into high molecular weight oligomers in many cell types (27,35). However, it is possible that caveolin-2 exerts cell-or tissue-specific functions in vivo as shown in caveolin-2 (Ϫ͞Ϫ) mice and that cultured cells do not accurately reflect the functions of caveolin-2 in vivo.…”

Section: Discussionmentioning

confidence: 91%

“…Recombinant adenoviruses containing the cDNA encoding caveolin-1 (Adcav-1) or ␤-galactosidase (Ad␤-gal) were generated as described (34). Adenoviral, myc-tagged caveolin-2 (Adcav-2) was obtained from Enrique Rodriguez-Boulan (Weill Medical College of Cornell University, New York), and was constructed as described (35).…”

Section: Construction Of Adenoviral Vectors and Transduction Of Cellsmentioning

confidence: 99%

The phosphorylation of caveolin-2 on serines 23 and 36 modulates caveolin-1-dependent caveolae formation

Sowa

Pypaert

Fulton

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

101

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Caveolin-1 and -2 are the two major coat proteins found in plasma membrane caveolae of most of cell types. Here, by using adenoviral transduction of either caveolin-1 or caveolin-2 or both isoforms into cells lacking both caveolins, we demonstrate that caveolin-2 positively regulates caveolin-1-dependent caveolae formation. More importantly, we show that caveolin-2 is phosphorylated in vivo at two serine residues and that the phosphorylation of caveolin-2 is necessary for its actions as a positive regulator of caveolin-1 during organelle biogenesis in prostate cancer cells. Mutation of the primary phosphorylation sites on caveolin-2, serine 23 and 36, reduces the number of plasmalemma-attached caveolae and increases the accumulation of noncoated vesicles, but does not affect trafficking of caveolin-2, interaction with caveolin-1 or its biophysical properties. Thus, the phosphorylation of caveolin-2 is a novel mechanism to regulate the dynamics of caveolae assembly.

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“…We used the clone of FRT cells stably expressing cav-1 (T2). The procedure for stable transfection of these cells has been described (21).…”

Section: Adenoviral Transduction Of Frt and Lncap Cells With Cav-1 Anmentioning

confidence: 99%

Distinction between signaling mechanisms in lipid rafts vs. caveolae

Sowa

Pypaert

Sessa

2001

Proc. Natl. Acad. Sci. U.S.A.

211

158

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The relative importance of lipid rafts vs. specialized rafts termed caveolae to influence signal transduction is not known. Here we show that in cells lacking caveolae, the dually acylated protein, endothelial nitric oxide synthase (eNOS), localizes to cholesterolrich lipid raft domains of the plasma membrane. In these cells, expression of caveolin-1 (cav-1) stimulates caveolae biogenesis, promotes the interaction of cav-1 with eNOS, and the inhibition of NO release from cells. Interestingly, in cells where cav-1 does not drive caveolae assembly, despite equal levels of cav-1 and eNOS and localization of both proteins to raft domains of the plasmalemma, the physical interaction of eNOS with cav-1 is dramatically less resulting in less inhibition of NO release. Thus, cav-1 concentrated in caveolae, not in rafts, is in closer proximity to eNOS and is necessary for negative regulation of eNOS function, thereby providing the first clear example of spatial regulation of signaling in this organelle that is distinct from raft domains.T he lipid raft hypothesis formulated more than 10 years ago (1), postulated the existence of lipid rafts as dynamic assemblies of cholesterol and sphingolipids in the plasma membrane. Caveolae are specialized lipid rafts because of the ability of caveolins to initiate caveolae biogenesis from raft-derived components. The proposed functions of rafts͞caveolae are diverse and somewhat controversial, including cholesterol transport (2, 3), endocytosis (4), potocytosis (5), and signal transduction (6-9). In addition, there is much confusion in the literature where the distinction among lipid rafts, flattened caveolae, or caveolae proper is less than clear, thus making it difficult to ascertain which cellular functions might be attributable to rafts, caveolae, or caveolins, per se.For example, because cholesterol-modifying drugs such as cyclodextrins remove cholesterol from plasmalemmal rafts and caveolae, these reagents cannot distinguish between signaling events occurring in these compartments. Moreover, from a biophysical perspective, it is unknown whether the curvature and structure of plasmalemma-attached caveolae with caveolin-1 (cav-1) as the coat protein or whether the presence of cav-1 protein in the plasma membrane, per se, is necessary for the effects of cav-1 on any target protein or function. This distinction is important because although cav-1 is the main structural protein of caveolae, it may also exist in lipid rafts without the formation of plasmalemma-attached caveolae (10), be found in the trans-Golgi network as originally described (9), or found in other organelles (11).Endothelial nitric-oxide synthase (eNOS) is a dually acylated signaling protein responsible for the production of nitric oxide (NO) in the cardiovascular system. N-myristoylated and cysteine palmitoylation of eNOS targets eNOS to the cytoplasmic face of the Golgi and to plasmalemmal caveolae. eNOS in these domains can interface with several aspects of signal transduction systems through direct interactions wi...

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Caveolin-2 Localizes to the Golgi Complex but Redistributes to Plasma Membrane, Caveolae, and Rafts when Co-expressed with Caveolin-1

Cited by 195 publications

References 32 publications

Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update

Regulation of heterotrimeric G-protein signaling by NDPK/NME proteins and caveolins: an update

The phosphorylation of caveolin-2 on serines 23 and 36 modulates caveolin-1-dependent caveolae formation

Distinction between signaling mechanisms in lipid rafts vs. caveolae

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