The Splitting of Hepatocyte Gap Junctions and Zonulae Occludentes With Hypertonic Disaccharides

Goodenough, Daniel A.; Gilula, Norton B.

doi:10.1083/jcb.61.3.575

Cited by 176 publications

(51 citation statements)

References 42 publications

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“…The fact that center-to-center values for aggregated particles in untreated Novikoff cultures average slightly less than 9-11 nm may be due to technical reasons or to an actual alteration of the 9-to 11-nm particle in conjunction with or subsequent to aggregation. In other systems, particles have been observed near the edges of junctions which appear larger than the actual junctional particles (23,28). However, more quantitative--data will be needed to confirm the role of the aggregates in coupling.…”

Section: Discussionmentioning

confidence: 99%

Gap Junction Formation Between Reaggregated Novikoff Hepatoma Cells

Johnson

Hammer

Sheridan

et al. 1974

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

189

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We have combined freeze-fracture and electrophysiological methods in a study of It has been suggested that the direct diffusion of small molecules between the interiors of adjacent cells could be an important factor in cellular homeostasis and even the regulation of growth and differentiation (1-3). This exchange of molecules is believed to occur through gap junctions (4-7), which are specializations of two closely apposed membranes (8), each containing an aggregate of intramembranous particles (9, 10). The particles are presumed to bridge the narrowed extracellular space of a gap junction amd may provide an intercytoplasmic pathway for diffusing molecules (6, 10).While many ultrastructural and physiological properties of gap junctions have been elucidated (1,11,12)

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Section: Discussionmentioning

confidence: 99%

Gap Junction Formation Between Reaggregated Novikoff Hepatoma Cells

Johnson

Hammer

Sheridan

et al. 1974

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

189

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“…Hypertonic extracellular solutions split hepatocyte and cardiac junctions (cf. Dewey and Barr, 1964;Goodenough and Gilula, 1974), and gap junctions separate in the presence of high concentrations of calcium chelators (Campbell and Albertini, 1981;Hirokawa and Heuser, 1982). While there is no reason to hypothesize large osmotic differences across the gap junction vesicles, abundant evidence indicates that cytoplasmic calcium activity is normally about 0.1 HM, less than that found necessary extracellularly to maintain contact between junctional membranes.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the fate of the gap junction depends on the medium used for the dissociation procedure, and perhaps also on the tissue examined. When the tissue is treated with hypertonic sucrose or solutions with calcium buffered to submicromolar levels with chelators, gap junctions of heart (Dewey and Barr, 1965) and liver (Goodenough and Gilula, 1974;Hirokawa and Heurser, 1982) apparently split along the region of cell contact, leaving "hemichannels' in membranes of each of the previously connected cells. Alternatively, when tissue is dissociated with peptidases and solutions with calcium concentrations in the range 1-20 MM, gap junctions of heart (Muir, 1967;Severs and Powell, 1980), exocrine pancreas (Amsterdam and Jamieson, 1974), and perhaps most other tissues remain attached to one of the previously connected cells, generally with remnants of the nonfunctional membrane of the other cell attached.…”

Section: From the Departments Of Neuroscience And Physiology Albert mentioning

confidence: 99%

Fate of intercellular junctions in isolated adult rat cardiac cells.

Mazet¹,

Wittenberg²,

Spray³

1985

Circulation Research

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SUMMARY. Freeze fracture and thin section techniques have revealed morphological changes in gap junctions and intercalated discs of adult rat myocytes following enzymatic dissociation. Cell separation leaves behind small vesicular remnants of formerly adjacent cells connected to the intact cell by gap junctions; in contrast, desmosomes cleave at the region of intercellular contact. Apparently, the next step in gap junction breakdown is intemalization of the remnants. In thin section, lanthanum penetration reveals that the cleft of some apparently internalized gap junctions is in contact with the sarcolemma, while that of others is not. In freeze fracture replicas, cytoplasmic gap junctions frequently possess hexagonally packed domains of E-face pits separated by smooth regions that may correspond to separations of membranes of internalized junctions found in thin section. Study of material maintained overnight at 37°C showed no surface junctional remnants; topologies of cytoplasmic gap junctions were generally complex, and concentric membrane vesicles were common. These observations suggest that enzymatic dissociation initiates a progressive, defined sequence of junctional intemalization that begins with attached cell remnants and may have as the last determinable step the separation into single membranes inside the intact cell. (CircRes 56:195-204, 1985)

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“…Additional studies have shown that docked connexons cannot be separated under physiological conditions (Goodenough and Gilula, 1974;Ghoshroy et al, 1995), suggesting that GJ degradation could occur via the internalization of complete double-membrane spanning GJ plaques. Structural and ultrastructural analyses of differentiating tissues and cells in culture have shown cytoplasmically located, double-membrane GJ vesicles that were termed annular gap junctions (AGJs; Ginzberg and Gilula, 1979;Larsen et al, 1979;Leach and Oliphant, 1984;Mazet et al, 1985;Jordan et al, 2001), leading to the hypothesis that AGJ vesicles represent internalized GJs.…”

Section: Introductionmentioning

confidence: 99%

Internalization of Large Double-Membrane Intercellular Vesicles by a Clathrin-dependent Endocytic Process

Piehl

Lehmann

Gumpert

et al. 2007

MBoC

156

233

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Beyond its well-documented role in vesicle endocytosis, clathrin has also been implicated in the internalization of large particles such as viruses, pathogenic bacteria, and even latex beads. We have discovered an additional clathrin-dependent endocytic process that results in the internalization of large, double-membrane vesicles at lateral membranes of cells that are coupled by gap junctions (GJs). GJ channels bridge apposing cell membranes to mediate the direct transfer of electrical currents and signaling molecules from cell to cell. Here, we report that entire GJ plaques, clusters of GJ channels, can be internalized to form large, double-membrane vesicles previously termed annular gap junctions (AGJs). These internalized AGJ vesicles subdivide into smaller vesicles that are degraded by endo/lysosomal pathways. Mechanistic analyses revealed that clathrin-dependent endocytosis machinery-components, including clathrin itself, the alternative clathrin-adaptor Dab2, dynamin, myosin-VI, and actin are involved in the internalization, inward movement, and degradation of these large, intercellular double-membrane vesicles. These findings contribute to the understanding of clathrin's numerous emerging functions. INTRODUCTIONThe role of clathrin in endocytosis is well documented. This protein forms a typical curved lattice around endocytic vesicles that are internalized at the plasma membrane (PM). In addition, the involvement of clathrin in several uncharacteristic endocytic processes has been reported, including the internalization of viruses, pathogenic bacteria, and large latex beads (Aggeler and Werb, 1982;Ehrlich et al., 2004;Rust et al., 2004;Veiga and Cossart, 2005). Here, we describe another function of the clathrin-dependent endocytic machinery that results in the internalization of large, doublemembrane vesicles at lateral PMs of cells that are coupled by gap junctions (GJs).GJs are ubiquitously distributed channels that connect the cytoplasms of two apposing cells each participating in this connection via a half channel termed a connexon to provide direct cell-to-cell communication. Connexons are hexamers of four-pass membrane proteins called connexins (Cxs;Bruzzone et al., 1996;Kumar and Gilula, 1996). Once transported to the PM, GJ channels cluster into two-dimensional arrays termed plaques that can be composed of a few to many thousands of individual channels and vary from a few square nanometers to many square micrometers (Bruzzone et al., 1996; Falk, 2000a;Severs et al., 2001). GJ channels can open and close (gate) and physiological parameters, including intracellular pH, Ca 2ϩ concentration, and Cx phosphorylation, are known to modulate GJ channel gating and the extent of GJ-mediated intercellular coupling (Delmar et al., 2004;Lampe and Lau, 2004;Moreno, 2005). However, the extent of intercellular coupling could also be regulated through altering the number of GJ channels in the PM.Cxs have a surprisingly short half-life of only 1-5 h, leading to a rapid GJ and Cx protein turnover (Fallon and Goodeno...

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The Splitting of Hepatocyte Gap Junctions and Zonulae Occludentes With Hypertonic Disaccharides

Cited by 176 publications

References 42 publications

Gap Junction Formation Between Reaggregated Novikoff Hepatoma Cells

Gap Junction Formation Between Reaggregated Novikoff Hepatoma Cells

Fate of intercellular junctions in isolated adult rat cardiac cells.

Internalization of Large Double-Membrane Intercellular Vesicles by a Clathrin-dependent Endocytic Process

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