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The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis.

Standard

The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis. / Friedrich, Ulrike; Stöhr, Heidi; Hilfinger, Daniela; Loenhardt, Thomas; Schachner, Melitta; Langmann, Thomas; Weber, Bernhard H F.

in: HUM MOL GENET, Jahrgang 20, Nr. 6, 6, 2011, S. 1132-1142.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Friedrich, U, Stöhr, H, Hilfinger, D, Loenhardt, T, Schachner, M, Langmann, T & Weber, BHF 2011, 'The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis.', HUM MOL GENET, Jg. 20, Nr. 6, 6, S. 1132-1142. <http://www.ncbi.nlm.nih.gov/pubmed/21196491?dopt=Citation>

APA

Friedrich, U., Stöhr, H., Hilfinger, D., Loenhardt, T., Schachner, M., Langmann, T., & Weber, B. H. F. (2011). The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis. HUM MOL GENET, 20(6), 1132-1142. [6]. http://www.ncbi.nlm.nih.gov/pubmed/21196491?dopt=Citation

Vancouver

Friedrich U, Stöhr H, Hilfinger D, Loenhardt T, Schachner M, Langmann T et al. The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis. HUM MOL GENET. 2011;20(6):1132-1142. 6.

Bibtex

@article{c940d398863341e6a0eb660843e4c33b,
title = "The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis.",
abstract = "Mutations in the RS1 gene that encodes the discoidin domain containing retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular degeneration in males. Disorganization of retinal layers and electroretinogram abnormalities are hallmarks of the disease and are also found in mice deficient for the orthologous murine protein, indicating that retinoschisin is important for the maintenance of retinal cell integrity. Upon secretion, retinoschisin associates with plasma membranes of photoreceptor and bipolar cells, although the components by which the protein is linked to membranes in vivo are still unclear. Here, we show that retinoschisin fails to bind to phospholipids or unilamellar lipid vesicles. A recent proteomic approach identified the Na/K-ATPase subunits ATP1A3 and ATP1B2 as binding partners of retinoschisin. We analyzed mice deficient for retinoschisin (Rs1h(-/Y)) and ATP1B2 (Atp1b2(-/-)) to characterize the role of Na/K-ATPase interaction in the organization of retinoschisin on cellular membranes. We demonstrate that both the Na/K-ATPase and retinoschisin are significantly reduced in Atp1b2(-/-) retinas, suggesting that retinoschisin membrane association is severely impaired in the absence of ATP1A3 and ATP1B2 subunits. Conversely, the presence of ATP1A3 and ATP1B2 are obligatory for binding of exogenously applied retinoschisin to crude membranes. Also, co-expression of ATP1A3 and ATP1B2 is required for retinoschisin binding to intact Hek293 cells. Taken together, our data support a predominant role of Na/K-ATPase in anchoring retinoschisin to retinal cell surfaces. Furthermore, altered localization of ATP1A3 and ATP1B2 is a notable consequence of retinoschisin deficiency and thus may be an important downstream aspect of cellular pathology in XLRS.",
keywords = "Animals, Humans, Male, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Transport, Cell Line, Protein Binding, HEK293 Cells, Adenosine Triphosphatases/genetics/*metabolism, Cation Transport Proteins/genetics/*metabolism, Cell Adhesion Molecules/*deficiency/genetics, Cell Adhesion Molecules, Neuronal/genetics/*metabolism, Cell Membrane/genetics/*metabolism, Eye Proteins/genetics, Phospholipids/metabolism, Retinoschisis/*enzymology/genetics/metabolism, Sodium-Potassium-Exchanging ATPase/genetics/*metabolism, Animals, Humans, Male, Female, Mice, Mice, Inbred C57BL, Mice, Knockout, Protein Transport, Cell Line, Protein Binding, HEK293 Cells, Adenosine Triphosphatases/genetics/*metabolism, Cation Transport Proteins/genetics/*metabolism, Cell Adhesion Molecules/*deficiency/genetics, Cell Adhesion Molecules, Neuronal/genetics/*metabolism, Cell Membrane/genetics/*metabolism, Eye Proteins/genetics, Phospholipids/metabolism, Retinoschisis/*enzymology/genetics/metabolism, Sodium-Potassium-Exchanging ATPase/genetics/*metabolism",
author = "Ulrike Friedrich and Heidi St{\"o}hr and Daniela Hilfinger and Thomas Loenhardt and Melitta Schachner and Thomas Langmann and Weber, {Bernhard H F}",
year = "2011",
language = "English",
volume = "20",
pages = "1132--1142",
journal = "HUM MOL GENET",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - The Na/K-ATPase is obligatory for membrane anchorage of retinoschisin, the protein involved in the pathogenesis of X-linked juvenile retinoschisis.

AU - Friedrich, Ulrike

AU - Stöhr, Heidi

AU - Hilfinger, Daniela

AU - Loenhardt, Thomas

AU - Schachner, Melitta

AU - Langmann, Thomas

AU - Weber, Bernhard H F

PY - 2011

Y1 - 2011

N2 - Mutations in the RS1 gene that encodes the discoidin domain containing retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular degeneration in males. Disorganization of retinal layers and electroretinogram abnormalities are hallmarks of the disease and are also found in mice deficient for the orthologous murine protein, indicating that retinoschisin is important for the maintenance of retinal cell integrity. Upon secretion, retinoschisin associates with plasma membranes of photoreceptor and bipolar cells, although the components by which the protein is linked to membranes in vivo are still unclear. Here, we show that retinoschisin fails to bind to phospholipids or unilamellar lipid vesicles. A recent proteomic approach identified the Na/K-ATPase subunits ATP1A3 and ATP1B2 as binding partners of retinoschisin. We analyzed mice deficient for retinoschisin (Rs1h(-/Y)) and ATP1B2 (Atp1b2(-/-)) to characterize the role of Na/K-ATPase interaction in the organization of retinoschisin on cellular membranes. We demonstrate that both the Na/K-ATPase and retinoschisin are significantly reduced in Atp1b2(-/-) retinas, suggesting that retinoschisin membrane association is severely impaired in the absence of ATP1A3 and ATP1B2 subunits. Conversely, the presence of ATP1A3 and ATP1B2 are obligatory for binding of exogenously applied retinoschisin to crude membranes. Also, co-expression of ATP1A3 and ATP1B2 is required for retinoschisin binding to intact Hek293 cells. Taken together, our data support a predominant role of Na/K-ATPase in anchoring retinoschisin to retinal cell surfaces. Furthermore, altered localization of ATP1A3 and ATP1B2 is a notable consequence of retinoschisin deficiency and thus may be an important downstream aspect of cellular pathology in XLRS.

AB - Mutations in the RS1 gene that encodes the discoidin domain containing retinoschisin cause X-linked juvenile retinoschisis (XLRS), a common macular degeneration in males. Disorganization of retinal layers and electroretinogram abnormalities are hallmarks of the disease and are also found in mice deficient for the orthologous murine protein, indicating that retinoschisin is important for the maintenance of retinal cell integrity. Upon secretion, retinoschisin associates with plasma membranes of photoreceptor and bipolar cells, although the components by which the protein is linked to membranes in vivo are still unclear. Here, we show that retinoschisin fails to bind to phospholipids or unilamellar lipid vesicles. A recent proteomic approach identified the Na/K-ATPase subunits ATP1A3 and ATP1B2 as binding partners of retinoschisin. We analyzed mice deficient for retinoschisin (Rs1h(-/Y)) and ATP1B2 (Atp1b2(-/-)) to characterize the role of Na/K-ATPase interaction in the organization of retinoschisin on cellular membranes. We demonstrate that both the Na/K-ATPase and retinoschisin are significantly reduced in Atp1b2(-/-) retinas, suggesting that retinoschisin membrane association is severely impaired in the absence of ATP1A3 and ATP1B2 subunits. Conversely, the presence of ATP1A3 and ATP1B2 are obligatory for binding of exogenously applied retinoschisin to crude membranes. Also, co-expression of ATP1A3 and ATP1B2 is required for retinoschisin binding to intact Hek293 cells. Taken together, our data support a predominant role of Na/K-ATPase in anchoring retinoschisin to retinal cell surfaces. Furthermore, altered localization of ATP1A3 and ATP1B2 is a notable consequence of retinoschisin deficiency and thus may be an important downstream aspect of cellular pathology in XLRS.

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Protein Transport

KW - Cell Line

KW - Protein Binding

KW - HEK293 Cells

KW - Adenosine Triphosphatases/genetics/metabolism

KW - Cation Transport Proteins/genetics/metabolism

KW - Cell Adhesion Molecules/deficiency/genetics

KW - Cell Adhesion Molecules, Neuronal/genetics/metabolism

KW - Cell Membrane/genetics/metabolism

KW - Eye Proteins/genetics

KW - Phospholipids/metabolism

KW - Retinoschisis/enzymology/genetics/metabolism

KW - Sodium-Potassium-Exchanging ATPase/genetics/metabolism

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Protein Transport

KW - Cell Line

KW - Protein Binding

KW - HEK293 Cells

KW - Adenosine Triphosphatases/genetics/metabolism

KW - Cation Transport Proteins/genetics/metabolism

KW - Cell Adhesion Molecules/deficiency/genetics

KW - Cell Adhesion Molecules, Neuronal/genetics/metabolism

KW - Cell Membrane/genetics/metabolism

KW - Eye Proteins/genetics

KW - Phospholipids/metabolism

KW - Retinoschisis/enzymology/genetics/metabolism

KW - Sodium-Potassium-Exchanging ATPase/genetics/metabolism

M3 - SCORING: Journal article

VL - 20

SP - 1132

EP - 1142

JO - HUM MOL GENET

JF - HUM MOL GENET

SN - 0964-6906

IS - 6

M1 - 6

ER -