Clathrin-independent internalization of normal cellular prion protein in neuroblastoma cells is associated with the Arf6 pathway

Kang, Young-Shin; Zhao, Xiaohong; Lovaas, Jenna D.; Eisenberg, Evan; Greene, Lois E.

doi:10.1242/jcs.046292

Cited by 29 publications

(27 citation statements)

References 35 publications

(63 reference statements)

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“…Similar to these ceramide derivatives, acetyl-C16-ceramide-NBD has a modified OH group in its structure; thus, we investigated the possible involvement of endocytosis on the uptake of acetyl-C16-ceramide-NBD. The initial step of endocytotic pathways at the plasma membrane is regulated by dynamin (35)(36)(37)(38). The expression of dynamin1K44A, a dominant-negative form of dynamin1, did not change the accumulation of acetyl-C16-ceramide-NBD in the Golgi complex.…”

Section: Possible Uptake Pathways Of Acetyl-c16-ceramide-nbdmentioning

confidence: 99%

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Makiyama

Nakamura

Nagasaka

et al. 2015

Traffic

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The Golgi complex plays a prominent role in the modification and sorting of lipids and proteins, and is a highly dynamic organelle that is dispersed and rearranged before and after mitosis. Several reagents including 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-C6-ceramide, a ceramide having an NBD-bound C6-N-acyl chain) and Golgi-specific proteins that emit fluorescence are used as Golgi markers. In the present study, we synthesized a new ceramide analog, acetyl-C16-ceramide-NBD (a ceramide having an acetylated C-1 hydroxyl group, C16-N-acyl chain, and NBD-bound C15-sphingosine), and showed that it preferentially accumulated in the Golgi complex without cytotoxicity for over 24 h. Pathways for cellular uptake and interorganelle trafficking of acetyl-C16-ceramide-NBD were investigated. Acetyl-C16-ceramide-NBD was transported to the Golgi complex via ceramide transport proteins. In contrast to NBD-C6-ceramide, acetyl-C16-ceramide-NBD was resistant to ceramide metabolic enzymes such as sphingomyelin synthase and glucosylceramide synthase. Because of its weaker cytotoxicity and resistance to ceramide metabolic enzymes, the localization of the Golgi complex could be observed in acetyl-C16-ceramide-NBD-labeled cells before and after mitosis. Lipids including sphingolipids play a structural role in the cellular membranes, and regulate physiological and pathological conditions in cells and tissues and in vivo by themselves. The backbone structure of sphingolipids including ceramide is sphingosine, and sphingosine-1-phosphate (S1P, the phosphate ester of the C-1 position of sphingosine) is an important signaling molecule (1,2). Ceramide, which has an N-acyl chain at the C-2 position of sphingosine, is a central point from where various sphingolipids are synthesized and interconverted. The hydroxyl (OH) † These authors contributed equally to this work.group at the C-1 position of ceramide is modified by various enzymes: phosphorylation by ceramide kinase and glucosylation by glucosylceramide (GlcCer) synthase produce ceramide-1-phosphate (C1P) and GlcCer, respectively. Sphingomyelin (SM) synthase transfers a phosphocholine head group from phosphatidylcholine to the OH group at the C-1 position of ceramide and produces SM.Many studies previously reported the usefulness of fluorescence-labeled ceramides and ceramide-related molecules in the study of uptake systems and the intracellular traffic of molecules. 4-Nitrobenzo-2-oxa-1, 476 www.traffic.dk

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Section: Possible Uptake Pathways Of Acetyl-c16-ceramide-nbdmentioning

confidence: 99%

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Makiyama

Nakamura

Nagasaka

et al. 2015

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“…Both, clathrin-dependent and -independent pathways have been described for PrP C internalization [54,59,62,63,64] (Figure 2). Although PrP C may be endocytosed through rafts in some cells [62,64,65], most studies demonstrate that PrP C translocates out of rafts prior to its internalization via clathrin-coated pits in permanent cell cultures and primary neurons [54,60,66,67,68,69].…”

Section: The Cellular Prion Protein Prpc: Structure Biosynthesis mentioning

confidence: 99%

“…Although PrP C may be endocytosed through rafts in some cells [62,64,65], most studies demonstrate that PrP C translocates out of rafts prior to its internalization via clathrin-coated pits in permanent cell cultures and primary neurons [54,60,66,67,68,69]. An amino-terminal, positively charged domain of PrP C is important for its endocytosis by clathrin-coated vesicles [54,66].…”

Section: The Cellular Prion Protein Prpc: Structure Biosynthesis mentioning

confidence: 99%

Cellular Aspects of Prion Replication In Vitro

Grassmann

Wolf

Hofmann

et al. 2013

Viruses

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Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered β-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and propagation of prions derived from cell culture experiments. We discuss recent findings on the trafficking of cellular and pathologic PrP, the potential sites of abnormal prion protein synthesis and potential co-factors involved in prion entry and propagation.

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“…Involvement of membrane rafts in infectious particle prion (PrP) infection has been reported [236][237][238][239][240][241][242]. PrP is an infectious protein that does not have a genome, unlike viruses.…”

Section: Role Of Membrane Rafts In Prion Infectionmentioning

confidence: 99%

Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

Takahashi

Suzuki

2011

Biochemistry Research International

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Membrane rafts are small (10–200 nm) sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Membrane rafts play an important role in viral infection cycles and viral virulence. Viruses are divided into four main classes, enveloped DNA virus, enveloped RNA virus, nonenveloped DNA virus, and nonenveloped RNA virus. General virus infection cycle is also classified into two sections, the early stage (entry process) and the late stage (assembly, budding, and release processes of virus particles). In the viral cycle, membrane rafts act as a scaffold of many cellular signal transductions, which are associated with symptoms caused by viral infections. In this paper, we describe the functions of membrane rafts in viral lifecycles and host cellular response according to each virus classification, each stage of the virus lifecycle, and each virus-induced signal transduction.

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Clathrin-independent internalization of normal cellular prion protein in neuroblastoma cells is associated with the Arf6 pathway

Cited by 29 publications

References 35 publications

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Cellular Aspects of Prion Replication In Vitro

Function of Membrane Rafts in Viral Lifecycles and Host Cellular Response

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