N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis

Magzoub, Mazin; Sandgren, Staffan; Lundberg, Pontus; Oglęcka, Kamila; Lilja, Johanna; Wittrup, Anders; Eriksson, Lars E.; Langel, Ülo; Belting, Mattias; Gräslund, Astrid

doi:10.1016/j.bbrc.2006.07.065

Cited by 92 publications

(66 citation statements)

References 33 publications

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“…However, these pathways might not be as general and could depend on the specific sequence of the CPP and the cargo attached to it. Several recent reports indicate that these peptides get inserted into the cell through endocytosis and pinocytosis [60][61][62][63][64]. We observed in our simulations that these peptides interact very strongly with the membrane, introducing lipid rearrangements and stress.…”

Section: Discussionsupporting

confidence: 52%

Cell Penetrating Peptides: How Do They Do It?

2007

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Cell penetrating peptides consist of short sequences of amino acids containing a large net positive charge that are able to penetrate almost any cell, carrying with them relatively large cargoes such as proteins, oligonucleotides, and drugs. During the 10 years since their discovery, the question of how they manage to translocate across the membrane has remained unanswered. The main discussion has been centered on whether they follow an energy-independent or an energy-dependent pathway. Recently, we have discovered the possibility of an energy-independent pathway that challenges fundamental concepts associated with protein-membrane interactions (Herce and Garcia, PNAS, 104: 20805 (2007) [1]). It involves the translocation of charged residues across the hydrophobic core of the membrane and the passive diffusion of these highly charged peptides across the membrane through the formation of aqueous toroidal pores. The aim of this review is to discuss the details of the mechanism and interpret some experimental results consistent with this view.

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Section: Discussionsupporting

confidence: 52%

Cell Penetrating Peptides: How Do They Do It?

2007

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“…Recently attention has been increasingly directed toward the molecular mechanism that regulates macropinocytosis, since some pathogenic bacteria such as Salmonella induce macropinocytosis to enter the host cells (Alpuche-Aranda et al, 1994;Terebiznik et al, 2002). It is also noteworthy that the bovine prion protein internalizes into mammalian cells mainly through macropinocytosis (Magzoub et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Effect of 3-methyladenine on the Fusion Process of Macropinosomes in EGF-stimulated A431 Cells

Araki

Hamasaki

Egami

et al. 2006

Cell Struct. Funct.

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ABSTRACT. In the process of receptor-mediated endocytosis, the fusion of endosomes in vitro is known to be inhibited by wortmannin or LY294002; inhibitors of phosphoinositide 3-kinase (PI3K), suggesting that the activity of PI3K is required for the fusion of early endosomes. In macropinocytosis, a process of bulk fluid-phase endocytosis, however, it remains unclear whether PI3K is required for the fusion of macropinosomes, since the macropinosome formation is inhibited by the PI3K inhibitors. In this study, we examined the effect of 3-methlyadenine (3-MA), which shows a distinct specificity to the PI3K classes from wortmannin and LY294002, on the macropinosome formation and fusion in EGF-stimulated A431 cells. Unlike wortmannin or LY294002, 3-MA did not inhibit the uptake of fluorescent dextran by macropinocytosis. However, the fusion of macropinosomes was inhibited by 3-MA. By imaging of live-cells expressing fluorescent protein-fused tandem FYVE domains, we found that PtdIns(3)P appeared on the macropinosomal membrane shortly after the closure of macropinocytic cups and remained on macropinosomes even at 60-min age. The production of PtdIns(3)P and the recruitment of EEA1 to macropinosomes were abolished by the 3-MA treatment. Therefore, it is likely that 3-MA impairs recruitment of EEA1 by inhibiting PtdIns(3)P production and resultantly blocks the fusion of macropinosomes. These results suggest that the local production of PtdIns(3)P implicates the fusion of macropinosomes via EEA1 as well as conventional early endosomes. However, the long association of PtdIns(3)P with macropinosomes may well be a cell-type specific feature of A431 cells.

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“…Immature dendritic cells and macrophages both continuously take up their surrounding fluid by macropinocytosis to sample their environment and capture antigens for presentation (8). Unfortunately this process can provide a way for pathogens to gain entry into host cells and is thus exploited by a number of infectious agents such as viruses, bacteria, and even prions (9)(10)(11)(12)(13).…”

mentioning

confidence: 99%

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley

Gopaldass

Bosmani

et al. 2016

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

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Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components.phagocytosis | macropinocytosis | WASH | Dictyostelium | trafficking

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N-terminal peptides from unprocessed prion proteins enter cells by macropinocytosis

Cited by 92 publications

References 33 publications

Cell Penetrating Peptides: How Do They Do It?

Cell Penetrating Peptides: How Do They Do It?

Effect of 3-methyladenine on the Fusion Process of Macropinosomes in EGF-stimulated A431 Cells

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

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