Endosome to Golgi Transport of Ricin Is Regulated by Cholesterol

Grimmer, Stine; Iversen, Tore Geir; Deurs, Bo van; Sandvig, Kirsten

doi:10.1091/mbc.11.12.4205

Cited by 103 publications

(104 citation statements)

References 40 publications

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“…These pathways include clathrin-dependent endocytosis, caveolae endocytosis, biogenesis of synaptic-like microvesicles, plasma membrane to Golgi apparatus, trans-Golgi network to apical surface, endosome to Golgi transport, recycling endosome-mediated transport, and yeast vacuole fusion (reviewed in Refs. [61][62][63]. Most of these transport systems are inhibited by modulation of the cholesterol content of the membranes.…”

Section: Discussionmentioning

confidence: 99%

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Stüven

Porat

Shimron

et al. 2003

Journal of Biological Chemistry

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Transport of proteins between intracellular membrane compartments is mediated by a protein machinery that regulates the budding and fusion processes of individual transport steps. Although the core proteins of both processes are defined at great detail, much less is known about the involvement of lipids. Here we report that changing the cellular balance of cholesterol resulted in changes of the morphology of the Golgi apparatus, accompanied by an inhibition of protein transport. By using a well characterized cell-free intra-Golgi transport assay, these observations were further investigated, and it was found that the transport reaction is sensitive to small changes in the cholesterol content of Golgi membranes. Addition as well as removal of cholesterol (10 ؎ 6%) to Golgi membranes by use of methyl-␤-cyclodextrin specifically inhibited the intra-Golgi transport assay. Transport inhibition occurred at the fusion step. Modulation of the cholesterol content changed the lipid raft partitioning of phosphatidylcholine and heterotrimeric G proteins, but not of other (non) lipid raft proteins and lipids. We suggest that the cholesterol balance in Golgi membranes plays an essential role in intra-Golgi protein transport and needs to be carefully regulated to maintain the structural and functional organization of the Golgi apparatus.

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Section: Discussionmentioning

confidence: 99%

Intra-Golgi Protein Transport Depends on a Cholesterol Balance in the Lipid Membrane

Stüven

Porat

Shimron

et al. 2003

Journal of Biological Chemistry

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“…The agent was applied simultaneously into the apical and basolateral chambers of the Transwell support. M␤CD saturated with cholesterol (m␤CD/chol) was prepared as previously described (Grimmer et al, 2000). Cholesterol enrichment of cellular membranes was achieved by treating the cells for 60 min at 37°C with 10 mM m␤CD/chol dissolved in MEM/Hanks' salts lacking BSA.…”

Section: Cholesterol Depletion and Enrichmentmentioning

confidence: 99%

Cholesterol-sensitive Modulation of Transcytosis

Leyt

Melamed-Book

Vaerman

et al. 2007

MBoC

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Cholesterol-rich membrane domains (e.g., lipid rafts) are thought to act as molecular sorting machines, capable of coordinating the organization of signal transduction pathways within limited regions of the plasma membrane and organelles. The significance of these domains in polarized postendocytic sorting is currently not understood. We show that dimeric IgA stimulates the incorporation of its receptor into cholesterol-sensitive detergent-resistant membranes confined to the basolateral surface/basolateral endosomes. A fraction of human transferrin receptor was also found in basolateral detergent-resistant membranes. Disrupting these membrane domains by cholesterol depletion (using methyl-␤-cyclodextrin) before ligand-receptor internalization caused depolarization of traffic from endosomes, suggesting that cholesterol in basolateral lipid rafts plays a role in polarized sorting after endocytosis. In contrast, cholesterol depletion performed after ligand internalization stimulated cargo transcytosis. It also stimulated caveolin-1 phosphorylation on tyrosine 14 and the appearance of the activated protein in dimeric IgA-containing apical organelles. We propose that cholesterol depletion stimulates the coupling of transcytotic and caveolin-1 signaling pathways, consequently prompting the membranes to shuttle from endosomes to the plasma membrane. This process may represent a unique compensatory mechanism required to maintain cholesterol balance on the cell surface of polarized epithelia. INTRODUCTIONIn humans, the major antibody that mediates immunological defense against mucosal infections is dimeric IgA (dIgA). This antibody is produced by plasma cells in the lamina propria located underneath the mucosal surface (reviewed in Lamm et al., 1995;Rojas and Apodaca, 2002) and is carried from the blood to mucosal secretions by the polymeric immunoglobulin receptor (pIgR). The itinerary of pIgR and its ligand was intensively studied in the polarized MadinDarby canine kidney (MDCK) cell line that heterologously expresses rabbit pIgR (for a recent review, see Rojas and Apodaca, 2002). The receptor is initially delivered from the trans-Golgi network (TGN) to the basolateral plasma membrane, where it encounters and binds dIgA. The complex is subsequently internalized and transcytosed to the apical plasma membrane of the cell. At that surface, the ectodomain of pIgR is proteolytically cleaved off to yield the secretory component (SC), which is released together with dIgA into mucosal secretions. In the course of transcytosis, pIgRdIgA complexes traverse various endosomal compartments, among which is an endocytic compartment located immediately underneath the apical surface (Gibson et al., 1998). This apical compartment, defined as apical recycling endosomes (AREs), is enriched in dIgA and is relatively deficient in recycling transferrin (Apodaca et al., 1994;Barroso and Sztul, 1994;Brown et al., 2000). AREs are thought to play a unique role in transcytosis, possibly by exploiting apical recycling mechanisms to shuttle transcy...

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“…24 Furthermore, the clathrin-independent endocytosis can be dependent on lipid rafts (domains rich in cholesterol and sphingolipids), 25 or it can be raftindependent. 26,27 Clathrin-independent endocytosis can also operate with 25 and without dynamin 26,27 as an essential molecule. Thus, clathrin-independent uptake of the IL2 receptor is dependent on lipid rafts, 25 whereas ricin and cholera toxin can be internalized under conditions where clathrin-dependent uptake is inhibited and cholesterol has been depleted from the rest of the membrane.…”

Section: Introductionmentioning

confidence: 99%