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Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects

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Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects. / Rujano, Maria A; Cannata Serio, Magda; Panasyuk, Ganna; Péanne, Romain; Reunert, Janine; Rymen, Daisy; Hauser, Virginie; Park, Julien H; Freisinger, Peter; Souche, Erika; Guida, Maria Clara; Maier, Esther M; Wada, Yoshinao; Jäger, Stefanie; Krogan, Nevan J; Kretz, Oliver; Nobre, Susana; Garcia, Paula; Quelhas, Dulce; Bird, Thomas D; Raskind, Wendy H; Schwake, Michael; Duvet, Sandrine; Foulquier, Francois; Matthijs, Gert; Marquardt, Thorsten; Simons, Matias.

In: J EXP MED, Vol. 214, No. 12, 04.12.2017, p. 3707-3729.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rujano, MA, Cannata Serio, M, Panasyuk, G, Péanne, R, Reunert, J, Rymen, D, Hauser, V, Park, JH, Freisinger, P, Souche, E, Guida, MC, Maier, EM, Wada, Y, Jäger, S, Krogan, NJ, Kretz, O, Nobre, S, Garcia, P, Quelhas, D, Bird, TD, Raskind, WH, Schwake, M, Duvet, S, Foulquier, F, Matthijs, G, Marquardt, T & Simons, M 2017, 'Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects', J EXP MED, vol. 214, no. 12, pp. 3707-3729. https://doi.org/10.1084/jem.20170453

APA

Rujano, M. A., Cannata Serio, M., Panasyuk, G., Péanne, R., Reunert, J., Rymen, D., Hauser, V., Park, J. H., Freisinger, P., Souche, E., Guida, M. C., Maier, E. M., Wada, Y., Jäger, S., Krogan, N. J., Kretz, O., Nobre, S., Garcia, P., Quelhas, D., ... Simons, M. (2017). Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects. J EXP MED, 214(12), 3707-3729. https://doi.org/10.1084/jem.20170453

Vancouver

Rujano MA, Cannata Serio M, Panasyuk G, Péanne R, Reunert J, Rymen D et al. Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects. J EXP MED. 2017 Dec 4;214(12):3707-3729. https://doi.org/10.1084/jem.20170453

Bibtex

@article{a4ea3454ab9e455fb3e6c7481371fdd1,
title = "Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects",
abstract = "The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.",
keywords = "Adolescent, Amino Acid Sequence, Animals, Autophagy, Base Sequence, Blood Proteins, Brain, Cutis Laxa, Drosophila Proteins, Drosophila melanogaster, Endoplasmic Reticulum-Associated Degradation, Fibroblasts, Genes, X-Linked, Glycosylation, Humans, Infant, Lipids, Liver, Liver Diseases, Male, Membrane Proteins, Mice, Mutation, Neural Stem Cells, Protein Binding, Protein Processing, Post-Translational, Proton-Translocating ATPases, Psychomotor Disorders, Receptors, Cell Surface, Vacuolar Proton-Translocating ATPases, Young Adult, Journal Article",
author = "Rujano, {Maria A} and {Cannata Serio}, Magda and Ganna Panasyuk and Romain P{\'e}anne and Janine Reunert and Daisy Rymen and Virginie Hauser and Park, {Julien H} and Peter Freisinger and Erika Souche and Guida, {Maria Clara} and Maier, {Esther M} and Yoshinao Wada and Stefanie J{\"a}ger and Krogan, {Nevan J} and Oliver Kretz and Susana Nobre and Paula Garcia and Dulce Quelhas and Bird, {Thomas D} and Raskind, {Wendy H} and Michael Schwake and Sandrine Duvet and Francois Foulquier and Gert Matthijs and Thorsten Marquardt and Matias Simons",
note = "{\textcopyright} 2017 Rujano et al.",
year = "2017",
month = dec,
day = "4",
doi = "10.1084/jem.20170453",
language = "English",
volume = "214",
pages = "3707--3729",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic defects

AU - Rujano, Maria A

AU - Cannata Serio, Magda

AU - Panasyuk, Ganna

AU - Péanne, Romain

AU - Reunert, Janine

AU - Rymen, Daisy

AU - Hauser, Virginie

AU - Park, Julien H

AU - Freisinger, Peter

AU - Souche, Erika

AU - Guida, Maria Clara

AU - Maier, Esther M

AU - Wada, Yoshinao

AU - Jäger, Stefanie

AU - Krogan, Nevan J

AU - Kretz, Oliver

AU - Nobre, Susana

AU - Garcia, Paula

AU - Quelhas, Dulce

AU - Bird, Thomas D

AU - Raskind, Wendy H

AU - Schwake, Michael

AU - Duvet, Sandrine

AU - Foulquier, Francois

AU - Matthijs, Gert

AU - Marquardt, Thorsten

AU - Simons, Matias

N1 - © 2017 Rujano et al.

PY - 2017/12/4

Y1 - 2017/12/4

N2 - The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.

AB - The biogenesis of the multi-subunit vacuolar-type H+-ATPase (V-ATPase) is initiated in the endoplasmic reticulum with the assembly of the proton pore V0, which is controlled by a group of assembly factors. Here, we identify two hemizygous missense mutations in the extracellular domain of the accessory V-ATPase subunit ATP6AP2 (also known as the [pro]renin receptor) responsible for a glycosylation disorder with liver disease, immunodeficiency, cutis laxa, and psychomotor impairment. We show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects. The introduction of one of the missense mutations into Drosophila led to reduced survival and altered lipid metabolism. We further demonstrate that in the liver-like fat body, the autophagic dysregulation was associated with defects in lysosomal acidification and mammalian target of rapamycin (mTOR) signaling. Finally, both ATP6AP2 mutations impaired protein stability and the interaction with ATP6AP1, a member of the V0 assembly complex. Collectively, our data suggest that the missense mutations in ATP6AP2 lead to impaired V-ATPase assembly and subsequent defects in glycosylation and autophagy.

KW - Adolescent

KW - Amino Acid Sequence

KW - Animals

KW - Autophagy

KW - Base Sequence

KW - Blood Proteins

KW - Brain

KW - Cutis Laxa

KW - Drosophila Proteins

KW - Drosophila melanogaster

KW - Endoplasmic Reticulum-Associated Degradation

KW - Fibroblasts

KW - Genes, X-Linked

KW - Glycosylation

KW - Humans

KW - Infant

KW - Lipids

KW - Liver

KW - Liver Diseases

KW - Male

KW - Membrane Proteins

KW - Mice

KW - Mutation

KW - Neural Stem Cells

KW - Protein Binding

KW - Protein Processing, Post-Translational

KW - Proton-Translocating ATPases

KW - Psychomotor Disorders

KW - Receptors, Cell Surface

KW - Vacuolar Proton-Translocating ATPases

KW - Young Adult

KW - Journal Article

U2 - 10.1084/jem.20170453

DO - 10.1084/jem.20170453

M3 - SCORING: Journal article

C2 - 29127204

VL - 214

SP - 3707

EP - 3729

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 12

ER -