Mechanism of recruiting Sec6/8 (exocyst) complex to the apical junctional complex during polarization of epithelial cells

Yeaman, Charles; Grindstaff, Kent K.; Nelson, W. James

doi:10.1242/jcs.00893

Cited by 175 publications

(207 citation statements)

References 68 publications

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“…Docking of apical transporters depends on the T-SNARE syntaxin 3 in MDCK cells (Low et al, 1996) and on a tetanus-insensitive V-SNARE (Galli et al, 1998;Low et al, 1998;Lafont et al, 1999). Docking of basolateral transporters requires syntaxin 4 (Low et al, 1996), rab 8 (Huber et al, 1993) and a V-SNARE, cellubrevin, which cooperates with AP-1B in basolateral membrane trafficking (Fields et al, 2007), as well as the exocyst (Grindstaff et al, 1998;Shipitsin and Feig, 2004; The EPP: machineries involved and their hijacking by cancer B Tanos and E Rodriguez-Boulan Yeaman et al, 2004b;Langevin et al, 2005), a multiprotein particle that is also a key regulator of yeast's secretory route (Potenza et al, 1992;TerBush and Novick, 1995;TerBush et al, 1996). Interestingly, the exocyst interacts with the clathrin adaptor AP1B (Folsch et al, 2003) and participates not only in biosynthetic delivery, but, also, in postendocytic recycling to both basolateral and apical membranes, the latter in association with the small GTPase Rab11a (Oztan et al, 2007).…”

Section: Polarized Trafficking Machinerymentioning

confidence: 99%

“…Upon establishment of cell-cell contacts, epithelial cells establish adherent junctions, a required step for the subsequent formation of TJ and for the reorganization of the cytoskeleton and of the polarized trafficking routes of epithelial cells (Cereijido et al, 2008;Miyoshi and Takai, 2005;Yeaman et al, 2004b) (Figure 1). The small GTPases Cdc42 and Rac1 are recruited and activated at the junctional region, where they coordinate the extracellular cues provided by adhesion molecules (E-cadherin, JAM and Nectins) with the activities of the polarity proteins (Figures 1 and 3a).…”

Section: D Organization Machinerymentioning

confidence: 99%

“…Downregulation of Cdc42 or expression of dominant negative mutants of Cdc42 results in aberrant lumen formation and accumulation of intracellular lumens or VACs (Martin-Belmonte et al, 2007) described earlier in the review (Figure 3b). Cdc42 also has important functions in polarized trafficking from the Golgi complex; it regulates differently the exit of apical and basolateral proteins from the TGN (Kroschewski et al, 1999;Cohen et al, 2001;Musch et al, 2001), presumably by organizing the local actin cytoskeleton at the perinuclear region (Kroschewski et al, 1999;Cohen et al, 2001;Musch et al, 2001) and through interactions with the exocyst Yeaman et al, 2004b) (Figures 1 and 3a).…”

Section: D Organization Machinerymentioning

confidence: 99%

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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%

Section: D Organization Machinerymentioning

confidence: 99%

Section: D Organization Machinerymentioning

confidence: 99%

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

2008

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“…Given the fact that a. claudins-1 and -2 from MDCK cells are recovered in low-density, TX-100 insoluble membrane fractions [43], and b. that the solubility patterns of TJ proteins in TX-100 and CHAPS are altered following CH depletion (Figs. 1 and 2), the possibility remains that these and other TJ proteins are components of CH-rich microdomains.…”

Section: The Buoyant Density Profile Of Tj Proteins Is Detergent Depementioning

confidence: 99%

Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin

Lynch

Francis

McCarthy

et al. 2007

Experimental Cell Research

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Differential centrifugation of Triton X-100 or CHAPS lysates from control and cholesterol (CH) depleted MDCK II cells, segregated integral tight junction (TJ) proteins associated with detergent resistant membranes (DRMs) into two groups. Group A proteins (occludin, claudin-2 and -3) were detected in large, intermediate and small aggregates in both detergents, whereas group B proteins (claudin-1, -4 and -7) were observed in small aggregates in TX-100 and in intermediate and small aggregates in CHAPS. Depletion of CH altered the distribution of group A and B proteins among the three size categories in a detergent-specific manner. In lysates produced with octyl glucoside, a detergent that selectively extracts proteins from DRMs, group A proteins were undetectable in large aggregates and CH depletion did not alter the distribution of either group A or B proteins in intermediate or small aggregates. Neither occludin (group A) nor claudin-1 (group B) was in intimate enough contact with CH to be cross-linked to [ 3 H]-photo-cholesterol. However, antibodies to either TJ protein co-immunoprecipitated caveolin-1, a CH-binding protein. Unlike claudins, occludin's presence in TJs and DRMs did not require palmitoylation. Equilibrium density centrifugation on discontinuous OptiPrep gradients revealed detergent-related differences in the densities of TJ-bearing DRMs. There was little or no change in those densities after CH depletion. Removing CH from the plasma membrane increased tyrosine and threonine phosphorylation of occludin, and transepithelial electrical resistance (TER) within 30 min. After 2 h of CH efflux, phospho-occludin levels and TER fell below control values. We conclude that the association of integral TJ proteins with DRMS, pelleted at low speeds, is partially CH dependent. However, the buoyant density of TJ-associated DRMs is a function of the detergent used and is insensitive to decreases in CH.

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“…Little is known about mechanisms underlying directional transport of basolateral vesicles following the TGN to the basolateral plasma membrane, although it is accepted that basolateral vesicles can be passively recruited by special structures such as the exocyst, t-SNARE/syntaxin4 or adhesion molecules (Yeaman et al, 2004). We used different strategies to elucidate an active role for Naked2 in this process.…”

Section: N-terminus Of Naked2 Confers Basolateral Directionalitymentioning

confidence: 99%

Naked2 Acts as a Cargo Recognition and Targeting Protein to Ensure Proper Delivery and Fusion of TGF-α–containing Exocytic Vesicles at the Lower Lateral Membrane of Polarized MDCK Cells

Li¹,

Hao

Cao³

et al. 2007

MBoC

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Transforming growth factor-␣ (TGF-␣) is the major autocrine EGF receptor ligand in vivo.In polarized epithelial cells, proTGF-␣ is synthesized and then delivered to the basolateral cell surface. We previously reported that Naked2 interacts with basolateral sorting determinants in the cytoplasmic tail of a Golgi-processed form of TGF-␣ and that TGF-␣ is not detected at the basolateral surface of Madin-Darby canine kidney (MDCK) cells expressing myristoylation-deficient (G2A) Naked2. By high-resolution microscopy, we now show that wild-type, but not G2A, Naked2-associated vesicles fuse at the plasma membrane. We further demonstrate that Naked2-associated vesicles are delivered to the lower lateral membrane of polarized MDCK cells independent of 1B adaptin. We identify a basolateral targeting segment within Naked2; residues 1-173 redirect NHERF-1 from the apical cytoplasm to the basolateral membrane, and internal deletion of residues 37-104 results in apical mislocalization of Naked2 and TGF-␣. Short hairpin RNA knockdown of Naked2 leads to a dramatic reduction in the 16-kDa cell surface isoform of TGF-␣ and increased cytosolic TGF-␣ immunoreactivity. We propose that Naked2 acts as a cargo recognition and targeting (CaRT) protein to ensure proper delivery, tethering, and fusion of TGF-␣-containing vesicles to a distinct region at the basolateral surface of polarized epithelial cells. INTRODUCTION All seven mammalian EGF receptor (EGFR) ligands (EGF, TGF-␣ [TGF␣], amphiregulin, heparin-binding EGF-like growth factor, betacellulin, epiregulin and epigen) are type 1 transmembrane proteins that are produced by many epithelial cell types (Harris et al., 2003). The fidelity of trafficking of these endogenous EGFR ligands to the proper cell surface in normal polarized epithelial cells is highly relevant since the EGFR is restricted to the basolateral membrane. TGF␣ is delivered preferentially to the basolateral cell surface of polarized epithelial cells where it is rapidly cleaved by TNF␣converting enzyme/a disintegrin and metalloprotease (TACE/ADAM-17;Dempsey and Coffey, 1994;Sunnarborg et al., 2002). Soluble TGF␣ is then avidly captured by basolateral EGFRs (Dempsey and Coffey, 1994). The rapid cleavage and avid capture of this ligand suggest that cell surface delivery may be a critical, and possibly rate-limiting, step in the posttranslational regulation of endogenous TGF␣ activity.Basolateral sorting information usually resides in the cytoplasmic tail of basolaterally targeted cargo. TGF␣'s cytoplasmic tail, the most highly conserved portion of the molecule across species, contains domains that affect its trafficking through the secretory pathway. The C-terminus contains a type 1 PDZ recognition domain (ETVV). The PDZ-containing proteins syntenin (Fernandez-Larrea et al., 1999), GRASP55 (Kuo et al., 2000), and membrane-associated guanylate kinase inverted (MAGI)-2 and -3 (Franklin et al., 2005) bind this motif early in the secretory pathway. This domain contributes to the efficiency, but not the fidelity, of trafficki...

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Mechanism of recruiting Sec6/8 (exocyst) complex to the apical junctional complex during polarization of epithelial cells

Cited by 175 publications

References 68 publications

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

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

Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin

Naked2 Acts as a Cargo Recognition and Targeting Protein to Ensure Proper Delivery and Fusion of TGF-α–containing Exocytic Vesicles at the Lower Lateral Membrane of Polarized MDCK Cells

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