Biogenesis of Caveolae: Stepwise Assembly of Large Caveolin and Cavin Complexes

Hayer, Arnold; Stoeber, Miriam; Bissig, Christin; Helenius, Ari

doi:10.1111/j.1600-0854.2009.01023.x

Cited by 236 publications

(361 citation statements)

References 60 publications

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“…Caveolin proteins are co-translationally inserted into the endoplasmic reticulum (ER) (4) and are delivered to the PM via the secretory pathway (5). Newly synthesized Cav1 molecules self-associate to form oligomers of 12 or 14 monomers (6,7). These oligomers then traffic from the Golgi apparatus to the PM via a vesicular carrier containing syntaxin 6, the ganglioside GM1, and glycosylphosphatidylinositollinked proteins (8).…”

Section: Edited By Dennis R Voelkermentioning

confidence: 99%

“…Although PtdSer-limiting manipulations are somewhat extreme, other physiological conditions do occur that result in the presence of non-caveolar Cav1. Cav1 is delivered to the PM via vesicular transport with Cav1 organized into oligomers of 12-14 monomers (6). Upon delivery to the plasma membrane, individual clusters will have to diffuse and collide with other clusters to form the larger caveolae.…”

Section: Non-caveolar Cav1-gfp Clusters Are Mobilementioning

confidence: 99%

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Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Hirama

Das

Yang

et al. 2017

Journal of Biological Chemistry

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Edited by Dennis R. VoelkerCaveolae are bulb-shaped nanodomains of the plasma membrane that are enriched in cholesterol and sphingolipids. They have many physiological functions, including endocytic transport, mechanosensing, and regulation of membrane and lipid transport. Caveola formation relies on integral membrane proteins termed caveolins (Cavs) and the cavin family of peripheral proteins. Both protein families bind anionic phospholipids, but the precise roles of these lipids are unknown. Here, we studied the effects of phosphatidylserine (PtdSer), phosphatidylinositol 4-phosphate (PtdIns4P), and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) on caveolar formation and dynamics. Using live-cell, single-particle tracking of GFP-labeled Cav1 and ultrastructural analyses, we compared the effect of PtdSer disruption or phosphoinositide depletion with caveola disassembly caused by cavin1 loss. We found that PtdSer plays a crucial role in both caveola formation and stability. Sequestration or depletion of PtdSer decreased the number of detectable Cav1-GFP puncta and the number of caveolae visualized by electron microscopy. Under PtdSer-limiting conditions, the co-localization of Cav1 and cavin1 was diminished, and cavin1 degradation was increased. Using rapamycin-recruitable phosphatases, we also found that the acute depletion of PtdIns4P and PtdIns (4,5)P 2 has minimal impact on caveola assembly but results in decreased lateral confinement. Finally, we show in a model of phospholipid scrambling, a feature of apoptotic cells, that caveola stability is acutely affected by the scrambling. We conclude that the predominant plasmalemmal anionic lipid PtdSer is essential for proper Cav clustering, caveola formation, and caveola dynamics and that membrane scrambling can perturb caveolar stability.

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Section: Edited By Dennis R Voelkermentioning

confidence: 99%

Section: Non-caveolar Cav1-gfp Clusters Are Mobilementioning

confidence: 99%

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Hirama

Das

Yang

et al. 2017

Journal of Biological Chemistry

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“…supplied by Ari Helenius 73 and Tamotsu Yoshimori, 74 respectively, and the control vector pmaxGFP from Lonza (VCA-1003).…”

Section: Transfection Of Small Interfering Rna (Sirna) and Plasmidsmentioning

confidence: 99%

Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia

et al. 2016

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(2016) Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia, Autophagy, 12:6, 1029-1046, DOI: 10.1080/15548627.2016 ABSTRACTAutophagy is an intracellular lysosomal degradation pathway where its primary function is to allow cells to survive under stressful conditions. Autophagy is, however, a double-edge sword that can either promote cell survival or cell death. In cancer, hypoxic regions contribute to poor prognosis due to the ability of cancer cells to adapt to hypoxia in part through autophagy. In contrast, autophagy could contribute to hypoxia induced cell death in cancer cells. In this study, we showed that autophagy increased during hypoxia. At 4 h of hypoxia, autophagy promoted cell survival whereas, after 48 h of hypoxia, autophagy increased cell death. Furthermore, we found that the tyrosine phosphorylation of EGFR (epidermal growth factor receptor) decreased after 16 h in hypoxia. Furthermore, EGFR binding to BECN1 in hypoxia was significantly higher at 4 h compared to 72 h. Knocking down or inhibiting EGFR resulted in an increase in autophagy contributing to increased cell death under hypoxia. In contrast, when EGFR was reactivated by the addition of EGF, the level of autophagy was reduced which led to decreased cell death. Hypoxia led to autophagic degradation of the lipid raft protein CAV1 (caveolin 1) that is known to bind and activate EGFR in a ligand-independent manner during hypoxia. By knocking down CAV1, the amount of EGFR phosphorylation was decreased in hypoxia and amount of autophagy and cell death increased. This indicates that the activation of EGFR plays a critical role in the switch between cell survival and cell death induced by autophagy in hypoxia.

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“…62,66 Near the plasma membrane, Cavs in the Cav-70S complexes are palmitoylated by palmitoyl acyltransferases and, after fusion with the plasma membrane, 62,67,68 cavin proteins aggregate on the cholesterol-rich and Cav-containing lipid rafts and thereby assist the formation of the membrane invaginations typical for caveolae. 62,69,70 The association of NDPK-B with Cav1 and Cav3 was first identified in the zebrafish. Knockdown of NDPK-B specifically caused not only the loss of NDPK-B and the associated heterotrimeric G proteins G s and G i , but also loss of the Cavs.…”

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

confidence: 99%

“…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%

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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Biogenesis of Caveolae: Stepwise Assembly of Large Caveolin and Cavin Complexes

Cited by 236 publications

References 60 publications

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Phosphatidylserine dictates the assembly and dynamics of caveolae in the plasma membrane

Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia

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

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