Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Kentaro Hanada
 + 1378 word(s) 1378 2022-03-04 12:07:58 |
2 Format correct
Vicky Zhou
 -1 word(s) 1377 2022-03-14 11:18:27 | |
3 Format correct
Vicky Zhou
 -3 word(s) 1375 2022-03-14 11:28:25 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Hanada, K. Ceramide Transport Protein CERT and Its Inhibitors. Encyclopedia. Available online: https://encyclopedia.pub/entry/20543 (accessed on 27 July 2024).
Hanada K. Ceramide Transport Protein CERT and Its Inhibitors. Encyclopedia. Available at: https://encyclopedia.pub/entry/20543. Accessed July 27, 2024.
Hanada, Kentaro. "Ceramide Transport Protein CERT and Its Inhibitors" Encyclopedia, https://encyclopedia.pub/entry/20543 (accessed July 27, 2024).
Hanada, K. (2022, March 14). Ceramide Transport Protein CERT and Its Inhibitors. In Encyclopedia. https://encyclopedia.pub/entry/20543
Hanada, Kentaro. "Ceramide Transport Protein CERT and Its Inhibitors." Encyclopedia. Web. 14 March, 2022.
Ceramide Transport Protein CERT and Its Inhibitors
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms23042098

Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. A potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. 

lipid transfer proteins sphingolipids Golgi apparatus CERT1 structure-based drug design off-target effects

1. Introduction

Lipids are the major constituents of all cell membranes and play dynamic roles in organelle structure and function. In eukaryotic cells, the endoplasmic reticulum (ER) is the main center for the synthesis of diverse types of lipids. Lipids newly synthesized in the ER are rapidly and accurately delivered to other organelles by a variety of lipid transfer proteins (LTPs), in a nonvesicular manner, at zones where the ER is in contact with other specific organelles [1][2][3][4][5][6]. Various viruses and obligate intracellular bacteria hijack Lipid transfer proteins (LTPs) of host cells for their proliferation [7][8][9][10]. Therefore, LTPs are fundamental for the metabolism of lipids and biogenesis of membrane compartments in cells and have been gaining attention as a novel type of molecular medicine target. Nonetheless, the repertoire of specific LTP inhibitors to date is limited.
Sphingolipids are a class of lipids that contain the long-chain amino alcohols termed sphingoid bases, including sphingosine, dihydrosphingosine, and phytosphingosine, as their structural backbone (Figure 1A). Sphingolipids are ubiquitous constituents of cell membranes in eukaryotes and also present in a limited number of prokaryote species [11][12][13][14]. Sphingolipids participate in various biological events, including cell growth, apoptosis, differentiation, and adhesion (reviewed in [15][16]). The choline-containing sphingophospholipid sphingomyelin is a ubiquitous and predominant type of sphingolipid found in mammals and is thought to be a chemically robust but noncovalently interactive type of phospholipid, unlike other types of phospholipid [11].
Figure 1. The de novo synthetic pathway for sphingomyelin. (A) Structure of mammalian sphingolipids. The chemical structures of three major sphingoid bases and several complex sphingolipids in mammalian cells are shown. Ceramide, sphingomyelin, and GlcCer are depicted as the N-palmitoyl sphingosine type, although there are various combinations of sphingoid bases and N-acyl chains in cells. (B) The de novo synthetic pathways for sphingomyelin and GlcCer in mammalian cells are shown. Solid arrows represent enzymatic reactions while dotted arrows represent inter-organelle transport processes. PtdCho, phosphatidylcholine.
In mammalian cells, sphingomyelin is mainly located in the plasma membrane (PM), although the Golgi apparatus (where sphingomyelin is synthesized) and endosomes/lysosomes (to which the PM-derived endocytosis is directed) also have sphingomyelin [17][18]. In the PM phospholipid bilayer, sphingomyelin is predominantly distributed in the exoplasmic leaflet, with less found in the cytoplasmic leaflet. Cytoplasm-oriented sphingomyelin was recently shown to be pivotal for forming a PM-derived, concave, tubular structure [19]. Sphingomyelin, in concert with cholesterol, generates nano-scale membrane domains (so-called “lipid rafts” or “detergent-resistant membranes”), in which the spatiotemporal confinement of various molecules needed for signaling and other dynamic events of membranes can efficiently occur (see [20][21] for recent reviews). Sphingomyelin may interact with specific membrane proteins as their functional modulator, while sphingomyelin is also an important metabolic reservoir for sphingolipid mediators such as ceramide, sphingosine, and sphingosine-1-phosphate, which are produced as catabolites of sphingomyelin (reviewed in [15][22][23][24]).
The ceramide transport protein CERT, a typical LTP, mediates the transport of ceramide from the ER to the Golgi apparatus, where ceramide is converted to sphingomyelin [11][25]. CERT was first discovered in 2003. In 2001, a ceramide-mimetic compound that potently inhibits ER-to-Golgi transport of ceramide in cells was serendipitously developed [26]; it was later shown to be a selective inhibitor of CERT [27]. Nevertheless, there was inevitable concern that natural ligand-mimetic compounds may directly bind to the desired target but also to various undesired targets that share the same natural ligand. Hence, ceramide-nonmimetic inhibitors have recently been developed using a structure-based drug design approach [28]. The establishment of a set of ligand-mimetic and nonmimetic inhibitors has provided a pharmacological tool to discriminate on-target effects from off-target effects.

2. Possible Applications of CERT Inhibitors

CERT plays a key role in the ceramide-sphingomyelin metabolic axis (reviewed in [11]). As more evidence has accumulated that ceramide and sphingomyelin participate in various physiological and pathophysiological events [15][16][23][24], more attention has been paid to CERT. Accordingly, it has been clarified that CERT and CERTL (also known as GPBPΔ26 and GPBP, respectively) participate in various events and functions in mammalian cells, including polyploid cancer cell death [29], EGF receptor signaling [30], lipotoxicity and glucolipotoxicity in islet β-cells [31][32], muscle insulin signaling [33], myofibril formation [34], integrity of glomerular basement membrane [35], cytotoxic autophagy [36], mitochondrial maintenance [37], and senescence [38].
Interest in CERT inhibitors has also been increasing, although it seems that CERT inhibitors have yet to be used clinically. One of the most desirable applications of CERT inhibitors may be their therapeutic use in cancer, because the upregulation of intracellular ceramide levels by the blockage of the ceramide-to-sphingomyelin conversion through the use of CERT inhibitors would facilitate the efficacy of existing anti-cancer drugs, as previously proposed [29]. For further possible applications of CERT inhibitors in the treatment of cancer, see the recent review by Chung et al. [39].
Another important application may be the therapeutic or prophylactic use of CERT inhibitors to treat disorders caused by abnormally activated CERT. Rapid advances in human clinical genetics studies have revealed that various specific missense mutations in the human CERT1 gene are associated with hereditary intellectual disabilities and mental development disorders with an autosomal dominant inheritance pattern [40][41][42][43][44], and some of these mutations were recently shown to compromise the functional repression of CERT [44][45]. Thus, a CERT inhibitor could be a rational tool to reduce abnormally activated CERT to a normal level. This could in turn improve the pathology of the CERT1 mutation-caused disease without shutting off the physiologically indispensable function of CERT, although more studies will be necessary to identify a clinically usable CERT inhibitor.
CERT1 encodes at least two CERT-related proteins, CERT/GPBPΔ26 and CERTL/GPBP, which are transcribed from different splicing transcripts. Revert et al. showed that CERTL/GPBP, but not CERT/GPBPΔ26, is exported from cells via a nonconventional secretion pathway [46]. Intriguingly, CERTL/GPBP was reported to be capable of binding various extracellular proteins including type IV collagen [47], serum amyloid P-component [48], the complement factor C1q [49], and the amyloid precursor protein and amyloid-β [50]. Thus, CERT inhibitors may also be a useful tool to investigate the physiological and pathophysiological significance of interactions between CERTL/GPBP and extracellular proteins, although it remains unclear whether the function of extracellular CERTL/GPBP is relevant to its ceramide-binding activity. Crivelli et al. recently revealed that genetically modified enhancement of CERTL expression in the brain in a familial Alzheimer’s disease model in mice reduces the amyloid-β level, accompanied by a decreasing ceramide level concomitant with increasing sphingomyelin level in the brain; they also found that administration of HPA-12 to the model mice for 4 weeks exacerbated the ceramide level and amyloid-β pathology [50]. Thus, long-term administration of a CERT inhibitor might aggravate Alzheimer’s disease. If ceramide-binding activity is also crucial to the function of extracellular CERTL/GPBP, then membrane-impermeable compounds, rather than membrane-permeable compounds, will be more appropriate to selectively modulate their extracellular function(s) without inhibiting their intracellular function(s).
The pharmacological or genetic inhibition of CERT negatively affects the proliferation of several types of intracellular pathogens, including hepatitis C virus [51][52][53], rubella virus [54], and the obligate intracellular bacterium Chlamydia [9][55][56]. Hence, CERT inhibitors might be applicable as anti-infectious disease agents, although pathogen genome-encoded factors, rather than human genome-encoded factors, may be more suitable molecular targets of anti-infectious disease drugs in terms of the risk of side effects.

References

  1. Hanada, K. Lipid transfer proteins rectify inter-organelle flux and accurately deliver lipids at membrane contact sites. J. Lipid Res. 2018, 59, 1341–1366. Correction in. J. Lipid Res. 2018, 59, 2034.
  2. Holthuis, J.C.; Menon, A.K. Lipid landscapes and pipelines in membrane homeostasis. Nature 2014, 510, 48–57.
  3. Wong, L.H.; Gatta, A.T.; Levine, T.P. Lipid transfer proteins: The lipid commute via shuttles, bridges and tubes. Nat. Rev. Mol. Cell Biol. 2019, 20, 85–101.
  4. Bohnert, M. Tether Me, Tether me not—Dynamic organelle contact sites in metabolic rewiring. Dev. Cell 2020, 54, 212–225.
  5. Reinisch, K.M.; Prinz, W.A. Mechanisms of nonvesicular lipid transport. J. Cell Biol. 2021, 220, e202012058.
  6. Cockcroft, S. Mammalian lipids: Structure, synthesis and function. Essays Biochem. 2021, 65, 813–845.
  7. Arita, M. Phosphatidylinositol-4 kinase III beta and oxysterol-binding protein accumulate unesterified cholesterol on poliovirus-induced membrane structure. Microbiol. Immunol. 2014, 58, 239–256.
  8. Bley, H.; Schöbel, A.; Herker, E. Whole Lotta Lipids—From HCV RNA Replication to the Mature Viral Particle. Int. J. Mol. Sci. 2020, 21, 2888.
  9. Derre, I.; Swiss, R.; Agaisse, H. The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS Pathog. 2011, 7, e1002092.
  10. Kumagai, K.; Elwell, C.A.; Ando, S.; Engel, J.N.; Hanada, K. Both the N- and C- terminal regions of the Chlamydial inclusion protein D (IncD) are required for interaction with the pleckstrin homology domain of the ceramide transport protein CERT. Biochem. Biophys. Res. Commun. 2018, 505, 1070–1076.
  11. Hanada, K. Co-evolution of sphingomyelin and the ceramide transport protein CERT. Biochim. Biophys. Acta 2014, 1841, 704–719. Correction in. Biochim. Biophys. Acta 2014, 1841, 1561–1562.
  12. Harrison, P.J.; Dunn, T.M.; Campopiano, D.J. Sphingolipid biosynthesis in man and microbes. Nat. Prod. Rep. 2018, 35, 921–954.
  13. Olea-Ozuna, R.J.; Poggio, S.; Quiroz-Rocha, E.; García-Soriano, D.A.; Sahonero-Canavesi, D.X.; Padilla-Gómez, J.; Martínez-Aguilar, L.; López-Lara, I.M.; Thomas-Oates, J.; Geiger, O. Five structural genes required for ceramide synthesis in Caulobacter and for bacterial survival. Environ. Microbiol. 2021, 23, 143–159.
  14. Stankeviciute, G.; Tang, P.; Ashley, B.; Chamberlain, J.D.; Hansen, M.E.; Coleman, A.; D’emilia, R.; Fu, L.; Mohan, E.C.; Nguyen, H. Convergent evolution of bacterial ceramide synthesis. Nat. Chem. Biol. 2021, 1–8.
  15. Hannun, Y.A.; Obeid, L.M. Sphingolipids and their metabolism in physiology and disease. Nat. Rev. Mol. Cell Biol. 2018, 19, 175–191.
  16. Dunn, T.M.; Tifft, C.J.; Proia, R.L. A perilous path: The inborn errors of sphingolipid metabolism. J. Lipid Res. 2019, 60, 475–483.
  17. Keenan, T.W.; Morre, D.J. Phospholipid class and fatty acid composition of Golgi apparatus isolated from rat liver and comparison with other cell fractions. Biochemistry 1970, 9, 19–25.
  18. Yachi, R.; Uchida, Y.; Balakrishna, B.H.; Anderluh, G.; Kobayashi, T.; Taguchi, T.; Arai, H. Subcellular localization of sphingomyelin revealed by two toxin-based probes in mammalian cells. Genes Cells 2012, 17, 720–727.
  19. Abe, M.; Makino, A.; Murate, M.; Hullin-Matsuda, F.; Yanagawa, M.; Sako, Y.; Kobayashi, T. PMP2/FABP8 induces PI (4, 5) P2-dependent transbilayer reorganization of sphingomyelin in the plasma membrane. Cell Rep. 2021, 37, 109935.
  20. Wang, H.-Y.; Bharti, D.; Levental, I. Membrane heterogeneity beyond the plasma membrane. Front. Cell Dev. Biol. 2020, 8, 580814.
  21. Sviridov, D.; Miller, Y.I. Biology of Lipid Rafts: Introduction to the Thematic Review Series. J. Lipid Res. 2020, 61, 598–600.
  22. Turpin-Nolan, S.M.; Brüning, J.C. The role of ceramides in metabolic disorders: When size and localization matters. Nat. Rev. Endocrinol. 2020, 16, 224–233.
  23. Tallima, H.; Azzazy, H.M.; El Ridi, R. Cell surface sphingomyelin: Key role in cancer initiation, progression, and immune evasion. Lipids Health Dis. 2021, 20, 150.
  24. Taniguchi, M.; Okazaki, T. Role of ceramide/sphingomyelin (SM) balance regulated through “SM cycle” in cancer. Cell. Signal. 2021, 87, 110119.
  25. Hanada, K.; Kumagai, K.; Yasuda, S.; Miura, Y.; Kawano, M.; Fukasawa, M.; Nishijima, M. Molecular machinery for non-vesicular trafficking of ceramide. Nature 2003, 426, 803–809.
  26. Ueno, M.; Kitagawa, H.; Ishitani, H.; Yasuda, S.; Hanada, K.; Kobayashi, S. Catalytic enantioselective synthesis of a novel inhibitor of ceramide trafficking,(1R, 3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecanamide (HPA-12). Tetrahedron Lett. 2001, 42, 7863–7865.
  27. Kumagai, K.; Yasuda, S.; Okemoto, K.; Nishijima, M.; Kobayashi, S.; Hanada, K. CERT mediates intermembrane transfer of various molecular species of ceramides. J. Biol. Chem. 2005, 280, 6488–6495.
  28. Nakao, N.; Ueno, M.; Sakai, S.; Egawa, D.; Hanzawa, H.; Kawasaki, S.; Kumagai, K.; Suzuki, M.; Kobayashi, S.; Hanada, K. Natural ligand-nonmimetic inhibitors of the lipid-transfer protein CERT. Commun. Chem. 2019, 2, 20.
  29. Swanton, C.; Marani, M.; Pardo, O.; Warne, P.H.; Kelly, G.; Sahai, E.; Elustondo, F.; Chang, J.; Temple, J.; Ahmed, A.A.; et al. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell 2007, 11, 498–512.
  30. Heering, J.; Weis, N.; Holeiter, M.; Neugart, F.; Staebler, A.; Fehm, T.N.; Bischoff, A.; Schiller, J.; Duss, S.; Schmid, S.; et al. Loss of the ceramide transfer protein augments EGF receptor signaling in breast cancer. Cancer Res. 2012, 72, 2855–2866.
  31. Guo, J.; Zhu, J.X.; Deng, X.H.; Hu, X.H.; Zhao, J.; Sun, Y.J.; Han, X. Palmitate-induced inhibition of insulin gene expression in rat islet beta-cells involves the ceramide transport protein. Cell. Physiol. Biochem. 2010, 26, 717–728.
  32. Gjoni, E.; Brioschi, L.; Cinque, A.; Coant, N.; Islam, M.N.; Ng, C.K.; Verderio, C.; Magnan, C.; Riboni, L.; Viani, P.; et al. Glucolipotoxicity impairs ceramide flow from the endoplasmic reticulum to the Golgi apparatus in INS-1 beta-cells. PLoS ONE 2014, 9, e110875.
  33. Bandet, C.L.; Mahfouz, R.; Veret, J.; Sotiropoulos, A.; Poirier, M.; Giussani, P.; Campana, M.; Philippe, E.; Blachnio-Zabielska, A.; Ballaire, R.; et al. Ceramide Transporter CERT Is Involved in Muscle Insulin Signaling Defects Under Lipotoxic Conditions. Diabetes 2018, 67, 1258–1271.
  34. Revert-Ros, F.; López-Pascual, E.; Granero-Moltó, F.; Macías, J.; Breyer, R.; Zent, R.; Hudson, B.G.; Saadeddin, A.; Revert, F.; Blasco, R. Goodpasture antigen-binding protein (GPBP) directs myofibril formation: Identification of intracellular downstream effector 130-kDa GPBP-interacting protein (GIP130). J. Biol. Chem. 2011, 286, 35030–35043.
  35. Revert, F.; Merino, R.; Monteagudo, C.; Macias, J.; Peydró, A.; Alcácer, J.; Muniesa, P.; Marquina, R.; Blanco, M.; Iglesias, M. Increased Goodpasture antigen-binding protein expression induces type IV collagen disorganization and deposit of immunoglobulin A in glomerular basement membrane. Am. J. Pathol. 2007, 171, 1419–1430.
  36. Hernandez-Tiedra, S.; Fabrias, G.; Davila, D.; Salanueva, I.J.; Casas, J.; Montes, L.R.; Anton, Z.; Garcia-Taboada, E.; Salazar-Roa, M.; Lorente, M.; et al. Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization. Autophagy 2016, 12, 2213–2229.
  37. Wang, X.; Rao, R.P.; Kosakowska-Cholody, T.; Masood, M.A.; Southon, E.; Zhang, H.; Berthet, C.; Nagashim, K.; Veenstra, T.K.; Tessarollo, L.; et al. Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice. J. Cell Biol. 2009, 184, 143–158.
  38. Rao, R.P.; Scheffer, L.; Srideshikan, S.M.; Parthibane, V.; Kosakowska-Cholody, T.; Masood, M.A.; Nagashima, K.; Gudla, P.; Lockett, S.; Acharya, U.; et al. Ceramide transfer protein deficiency compromises organelle function and leads to senescence in primary cells. PLoS ONE 2014, 9, e92142.
  39. Chung, L.H.; Liu, D.; Liu, X.T.; Qi, Y. Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer. Int. J. Mol. Sci. 2021, 22, 13184.
  40. de Ligt, J.; Willemsen, M.H.; van Bon, B.W.; Kleefstra, T.; Yntema, H.G.; Kroes, T.; Vulto-van Silfhout, A.T.; Koolen, D.A.; de Vries, P.; Gilissen, C.; et al. Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 2012, 367, 1921–1929.
  41. Hamdan, F.F.; Srour, M.; Capo-Chichi, J.M.; Daoud, H.; Nassif, C.; Patry, L.; Massicotte, C.; Ambalavanan, A.; Spiegelman, D.; Diallo, O.; et al. De novo mutations in moderate or severe intellectual disability. PLoS Genet. 2014, 10, e1004772.
  42. The Deciphering Developmental Disorders Study. Large-scale discovery of novel genetic causes of developmental disorders. Nature 2015, 519, 223–228.
  43. Lelieveld, S.H.; Wiel, L.; Venselaar, H.; Pfundt, R.; Vriend, G.; Veltman, J.A.; Brunner, H.G.; Vissers, L.; Gilissen, C. Spatial Clustering of de Novo Missense Mutations Identifies Candidate Neurodevelopmental Disorder-Associated Genes. Am. J. Hum. Genet. 2017, 101, 478–484.
  44. Murakami, H.; Tamura, N.; Enomoto, Y.; Shimasaki, K.; Kurosawa, K.; Hanada, K. Intellectual disability-associated gain-of-function mutations in CERT1 that encodes the ceramide transport protein CERT. PLoS ONE 2020, 15, e0243980.
  45. Tamura, N.; Sakai, S.; Martorell, L.; Colome, R.; Mizuike, A.; Goto, A.; Ortigoza-Escobar, J.D.; Hanada, K. Intellectual-disability-associated mutations in the ceramide transport protein gene CERT1 lead to aberrant function and subcellular distribution. J. Biol. Chem. 2021, 297, 101338.
  46. Revert, F.; Ventura, I.; Martinez-Martinez, P.; Granero-Molto, F.; Revert-Ros, F.; Macias, J.; Saus, J. Goodpasture antigen-binding protein is a soluble exportable protein that interacts with type IV collagen. Identification of novel membrane-bound isoforms. J. Biol. Chem. 2008, 283, 30246–30255.
  47. Raya, A.; Revert, F.; Navarro, S.; Saus, J. Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen. J. Biol. Chem. 1999, 274, 12642–12649.
  48. Mencarelli, C.; Bode, G.H.; Losen, M.; Kulharia, M.; Molenaar, P.C.; Veerhuis, R.; Steinbusch, H.W.; De Baets, M.H.; Nicolaes, G.A.; Martinez-Martinez, P. Goodpasture antigen-binding protein/ceramide transporter binds to human serum amyloid P-component and is present in brain amyloid plaques. J. Biol. Chem. 2012, 287, 14897–14911.
  49. Bode, G.H.; Losen, M.; Buurman, W.A.; Veerhuis, R.; Molenaar, P.C.; Steinbusch, H.W.; De Baets, M.H.; Daha, M.R.; Martinez-Martinez, P. Complement activation by ceramide transporter proteins. J. Immunol. 2014, 192, 1154–1161.
  50. Crivelli, S.M.; Luo, Q.; Stevens, J.A.A.; Giovagnoni, C.; van Kruining, D.; Bode, G.; den Hoedt, S.; Hobo, B.; Scheithauer, A.L.; Walter, J.; et al. CERTL reduces C16 ceramide, amyloid-beta levels, and inflammation in a model of Alzheimer’s disease. Alzheimers Res. Ther. 2021, 13, 45.
  51. Aizaki, H.; Morikawa, K.; Fukasawa, M.; Hara, H.; Inoue, Y.; Tani, H.; Saito, K.; Nishijima, M.; Hanada, K.; Matsuura, Y.; et al. Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection. J. Virol. 2008, 82, 5715–5724.
  52. Amako, Y.; Syed, G.H.; Siddiqui, A. Protein kinase D negatively regulates hepatitis C virus secretion through phosphorylation of oxysterol-binding protein and ceramide transfer protein. J. Biol. Chem. 2011, 286, 11265–11274.
  53. Gewaid, H.; Aoyagi, H.; Arita, M.; Watashi, K.; Suzuki, R.; Sakai, S.; Kumagai, K.; Yamaji, T.; Fukasawa, M.; Kato, F. Sphingomyelin is essential for the structure and function of the double-membrane vesicles in hepatitis C virus RNA replication factories. J. Virol. 2020, 94, e01080-20.
  54. Otsuki, N.; Sakata, M.; Saito, K.; Okamoto, K.; Mori, Y.; Hanada, K.; Takeda, M. Both sphingomyelin and cholesterol in the host cell membrane are essential for Rubella virus entry. J. Virol. 2017, 92, e01130-17.
  55. Elwell, C.A.; Jiang, S.; Kim, J.H.; Lee, A.; Wittmann, T.; Hanada, K.; Melancon, P.; Engel, J.N. Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog. 2011, 7, e1002198. Correction in. PLoS Pathog. 2013, 9.
  56. Tachida, Y.; Kumagai, K.; Sakai, S.; Ando, S.; Yamaji, T.; Hanada, K. Chlamydia trachomatis-infected human cells convert ceramide to sphingomyelin without sphingomyelin synthases 1 and 2. FEBS Lett. 2020, 594, 519–529.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biochemistry & Molecular Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Kentaro Hanada
View Times: 526
Revisions: 3 times (View History)
Update Date: 14 Mar 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback