High Cell Sensitivity to<i>Helicobacter pylori</i>VacA Toxin Depends on a GPI-anchored Protein and is not Blocked by Inhibition of the Clathrin-mediated Pathway of Endocytosis

Ricci, Vittorio; Galmiche, Antoine; Doye, Anne; Necchi, Vittorio; Solcia, Enrico; Boquet, Patrice

doi:10.1091/mbc.11.11.3897

Cited by 149 publications

(182 citation statements)

References 78 publications

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“…The subsequent intracellular route is dependent on the cell type, and lipid composition of lipid rafts seems crucial for sorting of intracellular trafficking. Certain bacterial toxins which are active intracellularly, such as Helicobacter pylori VacA (vacuolating toxin) (Ricci et al, 2000) and clostridial NTs (see below), recognize either GPI-anchored proteins or other molecules, but are associated with GPI-anchored proteins as receptors, and enter a specific intracellular pathway. In addition, toxins interacting with GPI-anchored proteins on the cell surface, such as aerolysin, have been used as tools to monitor the sorting of endocytic routes (Fivaz et al, 2002).…”

Section: Endocytic Pathway and Gpi (Glycosylphosphatidylinositol)-ancmentioning

confidence: 99%

Bacterial protein toxins and lipids: role in toxin targeting and activity

Geny

Popoff

2006

Biology of the Cell

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All bacterial toxins, which globally are hydrophilic proteins, interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Intracellular active toxins follow various trafficking pathways, the sorting of which is greatly dependent on the nature of the receptor, notably lipidic receptor or receptor embedded into a distinct environment such as lipid microdomains. Numerous other toxins act locally on cell membrane. Indeed, phospholipase activity is a common mechanism shared by several membrane‐damaging toxins. In addition, many toxins active intracellularly or on cell membrane modulate host cell phospholipid pathways. Unusually, a few bacterial toxins require a lipid post‐translational modification to be active. Thereby, lipids are obligate partners of bacterial toxins.

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Section: Endocytic Pathway and Gpi (Glycosylphosphatidylinositol)-ancmentioning

confidence: 99%

Bacterial protein toxins and lipids: role in toxin targeting and activity

Geny

Popoff

2006

Biology of the Cell

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“…In a variety of mammalian cell types (Skretting et al, 1999;Ricci et al, 2000;Fivaz et al, 2002) and in Drosophila hemocytes (Guha et al, 2003), GPI-anchored proteins continue to be internalized even when dynamin activity is inhibited. GPI-anchored proteins are then delivered to Rab5-negative GEECs.…”

Section: Introductionmentioning

confidence: 99%

“…In the absence of lateral associations of the type described above, or cross-linking and internalization through the caveolar/raft-dependent pathway (Nabi and Le, 2003), GPI-anchored proteins seem to be selectively internalized through a dynamin-independent pathway (Fivaz et al, 2002;Sabharanjak et al, 2002;Guha et al, 2003). It has been recently shown that the nanoscale organization of GPI-anchored proteins on the plasma membrane also influences their endocytic pathways (Sharma et al, 2004).In a variety of mammalian cell types (Skretting et al, 1999;Ricci et al, 2000;Fivaz et al, 2002) and in Drosophila hemocytes (Guha et al, 2003), GPI-anchored proteins continue to be internalized even when dynamin activity is inhibited. GPI-anchored proteins are then delivered to Rab5-negative GEECs.…”

mentioning

confidence: 99%

Arf6-independent GPI-anchored Protein-enriched Early Endosomal Compartments Fuse with Sorting Endosomes via a Rab5/Phosphatidylinositol-3′-Kinase–dependent Machinery

Kalia

Kumari

Chadda

et al. 2006

MBoC

107

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In the process of internalization of molecules from the extracellular milieu, a cell uses multiple endocytic pathways, consequently generating different endocytic vesicles. These primary endocytic vesicles are targeted to specific destinations inside the cell. Here, we show that GPI-anchored proteins are internalized by an Arf6-independent mechanism into GPI-anchored protein-enriched early endosomal compartments (GEECs). Internalized GPI-anchored proteins and the fluid phase are first visualized in GEECs that are acidic, primary endocytic structures, negative for early endosomal markers, Rab4, Rab5, and early endosome antigen (EEA)1. They subsequently acquire Rab5 and EEA1 before homotypic fusion with other GEECs, and heterotypic fusion with endosomes containing cargo from the clathrin-dependent endocytic pathway. Although, the formation of GEECs is unaffected by inhibition of Rab5 GTPase and phosphatidylinositol-3 -kinase (PI3K) activity, their fusion with sorting endosomes is dependent on both activities. Overexpression of Rab5 reverts PI3K inhibition of fusion, providing evidence that Rab5 effectors play important roles in heterotypic fusion between the dynamin-independent GEECs and clathrin-and dynamin-dependent sorting endosomes. INTRODUCTIONA cell uses multiple endocytic pathways for the uptake of molecules from the extracellular milieu (Mukherjee et al., 1997;Conner and Schmid, 2003). The better characterized pathways are mediated by clathrin-and caveolae-coated endocytic invaginations and require dynamin activity to be severed from the plasma membrane (Damke et al., 1994;Hinshaw and Schmid, 1995;Henley et al., 1998;Oh et al., 1998). There also seem to be one or more clathrin-independent pathways where dynamin is required, for example, the pathway for internalization of the interleukin (IL)-2 receptor subunits (Lamaze et al., 2001). In addition, there are a growing number of dynamin-independent endocytic processes that serve as internalization routes for a number of cell surface proteins, including lipid-linked proteins, such as GPI-anchored proteins (Lamaze and Schmid, 1995;Conner and Schmid, 2003;Nichols, 2003;Mayor and Riezman, 2004;Naslavsky et al., 2004;.GPI-anchored proteins are internalized via a dynamin, caveolin, and clathrin-independent pathway that is also responsible for the entry of a sizable fraction of the fluid phase in a number of cell types (Fivaz et al., 2002;Sabharanjak et al., 2002;Guha et al., 2003;. GPI-anchored proteins and the fluid phase enter the cell via tubular invaginations at the cell surface, into compartments termed GPI-anchored protein-enriched early endosomal compartments (GEECs) . At early times, these structures are largely devoid of cargo from the clathrin-dependent pathway. Besides a requirement for the small GTPase cdc42, very little is known about the molecular players that govern the formation and trafficking of GEECs. Much less is known about the detailed endocytic itinerary of these pathways (Lamaze and Schmid, 1995;Mayor and Riezman, 2004).After internalization...

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“…Intracellular expression of VacA by transient tranfection with VacA-encoding plasmids results in the formation of intracellular vacuoles that are indistinguishable from those that form when VacA is added to the outside of cells (29,30), suggesting that this toxin acts intracellularly. HEp-2 cells expressing dominant negative mutants of two proteins required for clathrin-dependent endocytosis (Eps 15 and dynamin II) develop cellular vacuoles in response to VacA (31), which suggests that VacA internalization can occur via a clathrin-independent endocytic pathway. It has been proposed that VacA toxicity requires localization of the toxin in either endosomes or mitochondria (28,32).…”

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confidence: 99%

“…In addition, certain bacterial toxins, including aerolysin, perfringolysin O, cholera toxin, and tetanus toxin, utilize rafts as either a site for high affinity binding and oligomerization on the surface of cells or as a site for internalization into host cells (42)(43)(44)(45)(46). A recent study reported that treatment of HEp-2 cells with phosphatidylinositol-specific phospholipase C (PI-PLC), an agent that removes GPIanchored proteins from the cell surface, inhibited the capacity of VacA to induce cell vacuolation (31). It also was reported that incubation of the cells with nystatin (a cholesterol-binding agent) inhibited VacA-induced cell vacuolation (31).…”

mentioning

confidence: 99%