Hensin Remodels the Apical Cytoskeleton and Induces Columnarization of Intercalated Epithelial Cells: Processes that Resemble Terminal Differentiation

Vijayakumar, S.; Takito, Jiro; Hikita, Chinami; Al‐Awqati, Qais

doi:10.1083/jcb.144.5.1057

Cited by 84 publications

(95 citation statements)

References 47 publications

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“…Such changes in morphology of microvilli have been reported in cells with decreased endocytosis (Vijayakumar et al, 1999); therefore it is not surprising to find these changes in the ␣ERKO male, which has already been shown to have decreased fluid reabsorption in the efferent ductules (Hess et al, 1997a). Actin filaments in microvilli apparently participate in the movement of membrane components into the endocytotic pits that form between microvilli (Gottlieb et al, 1993).…”

Section: Discussionmentioning

confidence: 65%

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

et al. 2001

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Lack of estrogen receptor (ER) results in fluid accumulation and dilation of the efferent ductules, suggesting that the role of estrogen and ER in the male reproductive tract is related to fluid reabsorption in the ductules. In the present study, endocytosis of the nonciliated cells of the efferent ductules was compared morphologically between wild type (WT) and estrogen receptor-␣ knockout (␣ERKO) male mice. The epithelial cells lining the WT efferent ductules were tall columnar in shape, whereas those of the ␣ERKO were low columnar. Immunocytochemically, the nonciliated cells of both genotypes showed positive reactions of sulfated glycoprotein-2, but the reaction products were reduced in amount in the ␣ERKO. Electron microscopy revealed that the nonciliated cells of the WT had numerous organelles for endocytosis such as coated pits and vesicles, tubules, endosomes, multivesicular bodies and lysosomes in the apical cytoplasm. These organelles were less developed in the nonciliated cells of the ␣ERKO. Morphometric analysis indicated that there was a significant reduction in area of endocytotic apparatus in the nonciliated cells of the ␣ERKO compared with that of the WT. A tracer study using gold particles demonstrated that the nonciliated cells of both WT and ␣ERKO efferent ductules were capable of taking up luminal contents. These results suggest that reabsorption of the luminal contents via endocytosis takes place in the efferent ductules but is greatly reduced in amount in the absence of ER␣.

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Section: Discussionmentioning

confidence: 65%

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

et al. 2001

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“…More recently, we discovered that low density cells were flat, and high density cells were columnar. Furthermore, the apical cytoskeleton was dramatically different in the two phenotypes; low density cells had sparse microvilli, no apical actin, villin, or cytokeratin 19, whereas high density cells had exuberant microvilli, abundant sub-apical actin, villin, and cytokeratin 19 (11). These studies show that the transition from ␤ to ␣ phenotype was remarkably similar to terminal differentiation of epithelia, especially as seen in the intestine during the transition from crypt to villus (12).…”

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confidence: 56%

Only Multimeric Hensin Located in the Extracellular Matrix Can Induce Apical Endocytosis and Reverse the Polarity of Intercalated Cells

Hikita

Takito

Vijayakumar

et al. 1999

Journal of Biological Chemistry

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When an intercalated epithelial cell line was seeded at low density and allowed to reach confluence, it located the anion exchanger band 3 in the apical membrane and an H ؉ -ATPase in the basolateral membrane. The same clonal cells seeded at high density targeted these proteins to the reverse location. Furthermore, high density cells had vigorous apical endocytosis, and low density cells had none. The extracellular matrix of high density cells was capable of inducing apical endocytosis and relocation of band 3 to the basolateral membrane in low density cells. A 230-kDa extracellular matrix (ECM) protein termed hensin, when purified to near-homogeneity, was able to reverse the phenotype of the low density cells. Antibodies to hensin prevented this effect, indicating that hensin is necessary for conversion of polarity. We show here that hensin was synthesized by both low density and high density cells. Whereas both phenotypes secreted soluble hensin into their media, only high density cells localized it in their ECM. Analysis of soluble hensin by sucrose density gradients showed that low density cells secreted monomeric hensin, and high density cells secreted higher order multimers. When 35 Slabeled monomeric hensin was added to high density cells, they induced its aggregation suggesting that the multimerization was catalyzed by surface events in the high density cells. Soluble monomeric or multimeric hensin did not induce apical endocytosis in low density cells, whereas the more polymerized hensin isolated from insoluble ECM readily induced it. These multimers could be disaggregated by sulfhydryl reagents and by dimethylmaleic anhydride, and treatment of high density ECM by these reagents prevented the induction of endocytosis. These results demonstrate that hensin, like several ECM proteins, needs to be precipitated in the ECM to be functional.The plasma membrane of epithelial cells is polarized into two domains; apical and basolateral, each of which has characteristic protein and lipid composition (1-3). Although targeting sequences were found in the structure of several polarized proteins, recent studies have shown that some proteins are polarized in a cell type-specific manner; for instance the Na,KATPase is targeted to the apical membrane of retinal pigment epithelium but to the basolateral membrane of most other epithelia (4). Several other proteins exhibit this flexibility in targeting; the most dramatic example is the targeting of the proton-translocating ATPase and the Cl:HCO 3 exchanger of the intercalated cell of the renal tubule (reviewed in Ref. 5). These cells exist in a spectrum of forms. One extreme, the ␣ type, has an apical H ϩ -ATPase and a basolateral anion exchanger that is an alternately spliced form of the erythroid band 3 (kAE1) 1 and hence is capable of trans-epithelial secretion of H ϩ . In contrast, the ␤ form secretes HCO 3 by a basolateral H ϩ -ATPase and an apical kAE1 (6). (However, one study did not find kAE1 by immunoblot analysis but confirmed the presence of its mRNA (7).) In an...

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“…Induction of apical endocytosis and the transport of an anion exchanger to the basolateral membrane clearly require an intact cytoskeleton. In addition, it had been demonstrated that β-intercalated cells are shorter and flatter than the α-phenotype (25), and effecting changes in cell shape depends on an intact cytoskeleton. We found that cytochalasin and colchicine, disrupters of actin and microtubules, respectively, both prevented the adaptive loss in apical Cl -/HCO 3 -exchange activity in response to acid incubation (Figure 3).…”

Section: Figurementioning

confidence: 99%

Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

Schwartz¹,

Tsuruoka²,

Vijayakumar³

et al. 2002

J. Clin. Invest.

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Hensin Remodels the Apical Cytoskeleton and Induces Columnarization of Intercalated Epithelial Cells: Processes that Resemble Terminal Differentiation

Cited by 84 publications

References 47 publications

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

Morphological analysis of endocytosis in efferent ductules of estrogen receptor‐α knockout male mouse

Only Multimeric Hensin Located in the Extracellular Matrix Can Induce Apical Endocytosis and Reverse the Polarity of Intercalated Cells

Acid incubation reverses the polarity of intercalated cell transporters, an effect mediated by hensin

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