Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity.

Wollner, Debra A.; Krzeminski, K A; Nelson, W. James

doi:10.1083/jcb.116.4.889

Cited by 97 publications

(58 citation statements)

References 61 publications

(91 reference statements)

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“…Since the E-cadherin mutations described here aect amino acid residues involved in Ca 2+ -binding, the diuse E-cadherin staining might be explained by a decreased ability to bind Ca 2+ , comparable to partial Ca 2+ -depletion. Diuse apical E-cadherin staining has also been described during the initial process of cell polarization when newly synthesized E-cadherin is ®rst delivered to the apical membrane, from which it is rapidly removed (Wollner et al, 1992). However, when polarization is complete, most E-cadherin is delivered directly to the lateral Tumour-associated mutations alter E-cadherin activity G Handschuh et al surface from the Golgi complex.…”

Section: Discussionmentioning

confidence: 99%

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

Handschuh¹,

Candidus

Luber³

et al. 1999

Oncogene

189

137

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A major function of the cell-to-cell adhesion molecule Ecadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin de®ciency in tumours leads to changes in cell morphology and motility, so that Ecadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that aect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L ®broblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing Ecadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin ®laments were drastically reduced. MDA-MB-435S cells with initial calciumdependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply aect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations aecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diuse type-gastric carcinomas.

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Section: Discussionmentioning

confidence: 99%

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

Handschuh¹,

Candidus

Luber³

et al. 1999

Oncogene

189

137

View full text Add to dashboard Cite

show abstract

“…Avner et al (ll), in an in vitro model of murine cyst formation by glucocorticoids in metanephric organ culture, found that treatment with the Na,KATPase blocking agent ouabain virtually eliminated cyst forma- : 2090 lo9 5% 10% 15% 10% 25% 30% 35% 40% 45% 50% Basolabral Peroxidase Steinins rapidly inactivated and then lost from the membrane (16). Retention in the basolateral membrane parallels retention of the cell adhesion molecule E-cadherin, which may be an essential co-factor in the assembly of anchored Na,K-ATPase units (17). A disturbance at the level of Na,K-ATPase retention appears to be the most likely explanation for our findings, but further study of relationship to anchoring proteins is required.…”

Section: Discussionmentioning

confidence: 99%

Renal tubule Na,K-ATPase polarity in glucocorticoid-induced polycystic kidney disease.

Ogborn¹,

Sareen²,

Grimm³

1993

J Histochem Cytochem.

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Cyst formation in polycystic kidney disease (PKD) involves proliferation of cyst lining epithelial and changes in trans-epithelial fluid and electrolyte transport. In vitro studies have suggested that mislocation of Na,K-ATPase to the apical tubular surface may be an important component of cyst fluid transport. We undertook in vivo studies of Na,K-ATPase location using the "threshold" murine model of glucocorticoid-induced PKD (GIPKD). Using histological, immunohistochemical, and densitometric techniques, we compared cyst formation and the cellular location of Na,K-ATPase in suckling C3H (low threshold for GIPKD) and DBA (high threshold) mice given an inducing dose of 200 mg/kg methylprednisolone acetate. As expected, C3H mice demonstrated greater cyst formation as measured by proportion of section area occupied by the tubule lumen (26.7% vs 15.5%; p < 0.001). Cyst formation was associated with increased Na,K-ATPase staining and increased apical Na,K-ATPase location. MPA treatment in C3H mice resulted in apical staining that exceeded basolateral staining (35.3% of reference window vs 29.8%; p < 0.001). The relatively GIPKD-resistant DBA mice did not show such change in Na,K-ATPase location. These immunohistochemical studies suggest a role for Na,K-ATPase in renal cyst formation.

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“…Cadherin-catenin complexes are involved in the establishment of cell polarity, 32 rearrangement of the cytoskeleton, 33 the formation of intercellular junctions, 34 and embryonic development. 35 A dominant negative, N-cadherin mutant mouse model showed reduced intercellular adhesion and increased cell migration, the loss of cell diVerentiation and polarisation, and early apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue

Barshack

Goldberg²,

Chowers³

et al. 2001

Journal of Clinical Pathology

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Background-Coeliac sprue is a chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves upon the withdrawal of wheat gliadins and related grain proteins from the diet. Biopsy specimens demonstrate diffuse enteritis with pronounced atrophy or total loss of villi. There is also a long term risk of malignant disease. Aims-To compare the immunoexpression of DCC (deleted in colon cancer), p53, E-cadherin, and -catenin in the duodenal mucosa of children with coeliac disease with that seen in children with no evidence of small intestinal disease. Methods-To gain more insight into the genetic and immunohistochemical alterations of the duodenal epithelium in coeliac disease, 21 endoscopic biopsies from children with coeliac disease and 10 duodenal biopsies from children without coeliac disease were immunohistochemically evaluated for p53, DCC, E-cadherin, and -catenin. Results-DCC expression was not reduced in patients with coeliac disease compared with those without coeliac disease. p53 positive nuclear immunostaining was seen in seven of the 21 patients with coeliac disease. Positive nuclear staining was seen mainly in the deep and the lateral aspects of the crypts. All patients in the control group were negative for p53. In nine and three of the 21 patients with coeliac disease, respectively, the immunohistochemical expression of E-cadherin and -catenin was reduced. However, both E-cadherin and -catenin immunostaining in the control group was not altered.Conclusions-E-cadherin and -catenin were reduced in the duodenal epithelium of children with coeliac disease when compared with normal mucosa. p53 was overexpressed in the duodenal mucosa of patients with coeliac disease. The reduced expression of E-cadherin and -catenin and p53 overexpression may contribute to the morphological changes seen in the small intestinal mucosa in coeliac disease. (J Clin Pathol 2001;54:684-688)

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Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity.

Cited by 97 publications

References 61 publications

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

Renal tubule Na,K-ATPase polarity in glucocorticoid-induced polycystic kidney disease.

Immunohistochemical analysis of candidate gene product expression in the duodenal epithelium of children with coeliac sprue

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