Definition of Distinct Compartments in Polarized Madin–Darby Canine Kidney (MDCK) Cells for Membrane‐Volume Sorting, Polarized Sorting and Apical Recycling

Brown, Paul S.; Wang, Exing; Aroeti, Benjamin; Chapin, Steven J.; Mostov, Keith E.; Dunn, Kenneth W.

doi:10.1034/j.1600-0854.2000.010205.x

Cited by 153 publications

(202 citation statements)

References 52 publications

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“…After arrival at the cell surface, apical and basolateral membrane proteins are internalized into separate apical sorting endosomes and basal sorting endosomes (Figure 2), (Breitfeld et al, 1989;Mostov et al, 2003;Rodriguez-Boulan et al, 2005), mixed in common recycling endosomes and sorted into distinct recycling routes back to their original PM domain. The apical recycling route includes the apical recycling endosome (Apodaca et al, 1994;Brown et al, 2000). More recent work has shown that some newly synthesized PM proteins move from TGN to common recycling endosomes and are sorted there in not fully polarized MDCK cells (Futter et al, 1995;Leitinger et al, 1995;Orzech et al, 2000;Ang et al, 2004;Cancino et al, 2007;Gravotta et al, 2007; reviewed by Ellis et al, 2006 Figure 1 The epithelial polarity program (EPP).…”

Section: Polarized Trafficking Machinerymentioning

confidence: 99%

The epithelial polarity program: machineries involved and their hijacking by cancer

2008

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The Epithelial Polarity Program (EPP) adapts and integrates three ancient cellular machineries to construct an epithelial cell. The polarized trafficking machinery adapts the cytoskeleton and ancestral secretory and endocytic machineries to the task of sorting and delivering different plasma membrane (PM) proteins to apical and basolateral surface domains. The domain-identity machinery builds a tight junctional fence (TJ) between apical and basolateral PM domains and adapts ancient polarity proteins and polarity lipids on the cytoplasmic side of the PM, which have evolved to perform a diversity of polarity tasks across cells and species, to provide 'identity' to each epithelial PM domain. The 3D organization machinery utilizes adhesion molecules as positional sensors of other epithelial cells and the basement membrane and small GTPases as integrators of positional information with the activities of the domain-identity and polarized trafficking machineries. Cancer is a disease mainly of epithelial cells (90% of human cancers are carcinomas that derive from epithelial cells) that hijacks the EPP machineries, resulting in loss of epithelial polarity, which often correlates in extent with the aggressiveness of the tumor. Here, we review how the EPP integrates its three machineries and the strategies used by cancer to hijack them.

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Section: Polarized Trafficking Machinerymentioning

confidence: 99%

The epithelial polarity program: machineries involved and their hijacking by cancer

2008

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“…This compartment was enriched in TfR and did not contain EEA1, a marker of early sorting endosomes (Wilson et al, 2000), or Rab11, a marker of AREs in MDCK cells (Casanova et al, 1999;Wang et al, 2001; Figure 2A). All of these characteristics are typical of a compartment denominated common RE, involved in the recycling of TfR and LDLR to the basolateral membrane and in the transcytosis of Polymeric IgA Receptor to the apical membrane via ARE (Futter et al, 1998;Brown et al, 2000;Wang et al, 2000). Additional experiments showed that the compartment decorated by 1Bn-Ab, unlike the TGN, was insensitive to tubulation induced by a kinase-dead form of PKD (Figure 3), a protein recently implicated in the regulation of the trafficking of basolateral proteins (Yeaman et al, 2004).…”

Section: Tgn-vs Ap1b-mediated Sorting Pathwaysmentioning

confidence: 99%

Antibody to AP1B Adaptor Blocks Biosynthetic and Recycling Routes of Basolateral Proteins at Recycling Endosomes

Cancino

Torrealba

Soza

et al. 2007

MBoC

117

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The epithelial-specific adaptor AP1B sorts basolateral plasma membrane (PM) proteins in both biosynthetic and recycling routes, but the site where it carries out this function remains incompletely defined. Here, we have investigated this topic in Fischer rat thyroid (FRT) epithelial cells using an antibody against the medium subunit 1〉. This antibody was suitable for immunofluorescence and blocked the function of AP1B in these cells. The antibody blocked the basolateral recycling of two basolateral PM markers, Transferrin receptor (TfR) and LDL receptor (LDLR), in a perinuclear compartment with marker and functional characteristics of recycling endosomes (RE). Live imaging experiments demonstrated that in the presence of the antibody two newly synthesized GFP-tagged basolateral proteins (vesicular stomatitis virus G [VSVG] protein and TfR) exited the trans-Golgi network (TGN) normally but became blocked at the RE within 3-5 min.By contrast, the antibody did not block trafficking of green fluorescent protein (GFP)-LDLR from the TGN to the PM but stopped its recycling after internalization into RE in ϳ45 min. Our experiments conclusively demonstrate that 1) AP1B functions exclusively at RE; 2) TGN-to-RE transport is very fast and selective and is mediated by adaptors different from AP1B; and 3) the TGN and AP1B-containing RE cooperate in biosynthetic basolateral sorting. INTRODUCTIONEpithelial cells display an asymmetric distribution of plasma membrane (PM) proteins into apical and basolateral PM domains (Yeaman et al., 1999;Mostov et al., 2003; RodriguezBoulan et al., 2005). Early studies demonstrated that this polarity was achieved by sorting of newly synthesized proteins at the level of the trans-Golgi network (TGN; Rindler et al., 1984;Fuller et al., 1985;Griffiths and Simons, 1986) and of endocytosed proteins at the level of recycling endosomes (RE;Mostov and Cardone, 1995;Odorizzi and Trowbridge, 1997). Trafficking in both biosynthetic and recycling routes is controlled by apical sorting signals (e.g., N-and O-glycans, lipid anchors, and protein domains with affinity for lipid rafts), by microtubule motor determinants (Rodriguez-Boulan and Gonzalez, 1999;Schuck and Simons, 2004;Rodriguez-Boulan et al., 2005) and by basolateral sorting signals (e.g., tyrosine, dileucine, and monoleucine motifs, some similar to endocytic determinants, and noncanonic motifs not yet matching any consensus sequence; Rodriguez-Boulan et al., 2005). Tyrosine-based signals are recognized by a family of organelle-specific tetrameric AP (adaptor protein) adaptors via their subunit, whereas dileucine motifs may be recognized via large (␥ and ␦) and small ( 1, 3) subunits of AP adaptors acting together (Bonifacino and Lippincott-Schwartz, 2003;Janvier et al., 2003).The early paradigm of two separate sorting sites for proteins in biosynthetic or recycling pathways has, however, progressively shifted over the past decade to a different paradigm in which both TGN and RE share a sorting role in the biosynthetic route. This new paradigm emer...

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“…MDCK and PTR-MDCK cells (MDCK coexpressing rabbit pIgR and hTfnR; Brown et al, 2000;Wang et al, 2000) were cultured routinely in 10-cm dishes, in minimal essential medium (MEM, Biological Industries) containing 5% fetal calf serum (Biological Industries) and 1% antibiotics (Biological Industries). To induce polarity, cells were cultured on polycarbonate filter supports (0.4-m pore size, Transwell, Costar, Cambridge, MA) for 4 d before each experiment (Aroeti et al, 1993).…”

Section: Cell Culturementioning

confidence: 99%

“…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 transcytotic cargo to the apical surface.…”

Section: Introductionmentioning

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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Definition of Distinct Compartments in Polarized Madin–Darby Canine Kidney (MDCK) Cells for Membrane‐Volume Sorting, Polarized Sorting and Apical Recycling

Cited by 153 publications

References 52 publications

The epithelial polarity program: machineries involved and their hijacking by cancer

The epithelial polarity program: machineries involved and their hijacking by cancer

Antibody to AP1B Adaptor Blocks Biosynthetic and Recycling Routes of Basolateral Proteins at Recycling Endosomes

Cholesterol-sensitive Modulation of Transcytosis

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