PMID- 29127204
OWN - NLM
STAT- MEDLINE
DCOM- 20171219
LR  - 20190619
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 214
IP  - 12
DP  - 2017 Dec 4
TI  - Mutations in the X-linked ATP6AP2 cause a glycosylation disorder with autophagic 
      defects.
PG  - 3707-3729
LID - 10.1084/jem.20170453 [doi]
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.
CI  - (c) 2017 Rujano et al.
FAU - Rujano, Maria A
AU  - Rujano MA
AUID- ORCID: 0000-0002-6859-3418
AD  - Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris, France.
AD  - Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France.
FAU - Cannata Serio, Magda
AU  - Cannata Serio M
AUID- ORCID: 0000-0002-2084-3406
AD  - Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris, France.
AD  - Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France.
FAU - Panasyuk, Ganna
AU  - Panasyuk G
AD  - Institut Necker-Enfants Malades, Paris, France.
AD  - Institut National de la Sante et de la Recherche Medicale U1151/Centre National 
      de la Recherche Scientifique UMR 8253, Paris, France.
FAU - Peanne, Romain
AU  - Peanne R
AUID- ORCID: 0000-0001-6077-4620
AD  - University of Leuven (KU Leuven), Center for Human Genetics, Leuven, Belgium.
FAU - Reunert, Janine
AU  - Reunert J
AD  - Universitatsklinikum Munster, Klinik fur Kinder- und Jugendmedizin, Munster, 
      Germany.
FAU - Rymen, Daisy
AU  - Rymen D
AUID- ORCID: 0000-0001-6628-3910
AD  - University of Leuven (KU Leuven), Center for Human Genetics, Leuven, Belgium.
FAU - Hauser, Virginie
AU  - Hauser V
AD  - Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris, France.
AD  - Institut National de la Sante et de la Recherche Medicale U1151/Centre National 
      de la Recherche Scientifique UMR 8253, Paris, France.
FAU - Park, Julien H
AU  - Park JH
AUID- ORCID: 0000-0003-2305-9948
AD  - Universitatsklinikum Munster, Klinik fur Kinder- und Jugendmedizin, Munster, 
      Germany.
FAU - Freisinger, Peter
AU  - Freisinger P
AD  - Kreiskliniken Reutlingen, Klinik fur Kinder- und Jugendmedizin, Klinikum am 
      Steinenberg, Reutlingen, Germany.
FAU - Souche, Erika
AU  - Souche E
AUID- ORCID: 0000-0001-9184-445X
AD  - University of Leuven (KU Leuven), Center for Human Genetics, Leuven, Belgium.
FAU - Guida, Maria Clara
AU  - Guida MC
AD  - Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris, France.
AD  - Institut National de la Sante et de la Recherche Medicale U1151/Centre National 
      de la Recherche Scientifique UMR 8253, Paris, France.
FAU - Maier, Esther M
AU  - Maier EM
AD  - Dr. von Haunersches Kinderspital der Universitat Munchen, Munchen, Germany.
FAU - Wada, Yoshinao
AU  - Wada Y
AD  - Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, 
      Japan.
FAU - Jager, Stefanie
AU  - Jager S
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, San Francisco, CA.
FAU - Krogan, Nevan J
AU  - Krogan NJ
AD  - Department of Cellular and Molecular Pharmacology, University of California, San 
      Francisco, San Francisco, CA.
FAU - Kretz, Oliver
AU  - Kretz O
AD  - Centre for Biological Signaling Studies BIOSS, University of Freiburg, Freiburg, 
      Germany.
FAU - Nobre, Susana
AU  - Nobre S
AUID- ORCID: 0000-0001-6749-8681
AD  - Metabolic Reference Center, Coimbra University Hospital Center, Coimbra, 
      Portugal.
FAU - Garcia, Paula
AU  - Garcia P
AUID- ORCID: 0000-0002-6847-745X
AD  - Metabolic Reference Center, Coimbra University Hospital Center, Coimbra, 
      Portugal.
FAU - Quelhas, Dulce
AU  - Quelhas D
AD  - Biochemical Genetics Unit, Centro de Genetica Medica Doutor Jacinto Magalhaes, 
      Centro Hospitalar do Porto, Abel Salazar Institute of Biomedical Sciences, 
      University of Porto, Porto, Portugal.
FAU - Bird, Thomas D
AU  - Bird TD
AD  - Department of Neurology, University of Washington, Seattle, WA.
AD  - Geriatric Research Center, Veterans Administration Medical Center, Seattle, WA.
FAU - Raskind, Wendy H
AU  - Raskind WH
AUID- ORCID: 0000-0001-8141-9054
AD  - Department of Medicine, University of Washington, Seattle, WA.
FAU - Schwake, Michael
AU  - Schwake M
AD  - Faculty of Chemistry/Biochemistry III, University Bielefeld, Bielefeld, Germany.
FAU - Duvet, Sandrine
AU  - Duvet S
AD  - Universite Lille, Centre National de la Recherche Scientifique UMR 8576, Unite de 
      Glycobiologie Structurale et Fonctionnelle, Lille, France.
FAU - Foulquier, Francois
AU  - Foulquier F
AD  - Universite Lille, Centre National de la Recherche Scientifique UMR 8576, Unite de 
      Glycobiologie Structurale et Fonctionnelle, Lille, France.
FAU - Matthijs, Gert
AU  - Matthijs G
AD  - University of Leuven (KU Leuven), Center for Human Genetics, Leuven, Belgium.
FAU - Marquardt, Thorsten
AU  - Marquardt T
AD  - Universitatsklinikum Munster, Klinik fur Kinder- und Jugendmedizin, Munster, 
      Germany.
FAU - Simons, Matias
AU  - Simons M
AUID- ORCID: 0000-0003-3959-6350
AD  - Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris, France 
      matias.simons@institutimagine.org.
AD  - Universite Paris Descartes-Sorbonne Paris Cite, Imagine Institute, Paris, France.
LA  - eng
SI  - RefSeq/NM_005765
GR  - R01 NS069719/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20171110
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (ATP6AP2 protein, Drosophila)
RN  - 0 (ATP6AP2 protein, human)
RN  - 0 (ATP6AP2 protein, mouse)
RN  - 0 (Blood Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Lipids)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
RN  - EC 3.6.3.14 (Proton-Translocating ATPases)
SB  - IM
CIN - Autophagy. 2018;14(6):1088-1089. PMID: 29388887
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Autophagy
MH  - Base Sequence
MH  - Blood Proteins/metabolism
MH  - Brain/embryology/pathology
MH  - Cutis Laxa/complications/pathology
MH  - Drosophila Proteins/*genetics/metabolism
MH  - Drosophila melanogaster/metabolism
MH  - Endoplasmic Reticulum-Associated Degradation
MH  - Fibroblasts/pathology
MH  - *Genes, X-Linked
MH  - Glycosylation
MH  - Humans
MH  - Infant
MH  - Lipids/chemistry
MH  - Liver/pathology
MH  - Liver Diseases/complications/pathology
MH  - Male
MH  - Membrane Proteins/*genetics/metabolism
MH  - Mice
MH  - Mutation/*genetics
MH  - Neural Stem Cells/cytology/metabolism
MH  - Protein Binding
MH  - Protein Processing, Post-Translational
MH  - Proton-Translocating ATPases/deficiency/*genetics/metabolism
MH  - Psychomotor Disorders/complications/pathology
MH  - Receptors, Cell Surface/chemistry/deficiency/*genetics/metabolism
MH  - Vacuolar Proton-Translocating ATPases/chemistry/deficiency/*genetics
MH  - Young Adult
PMC - PMC5716037
EDAT- 2017/11/12 06:00
MHDA- 2017/12/20 06:00
PMCR- 2018/06/04
CRDT- 2017/11/12 06:00
PHST- 2017/03/10 00:00 [received]
PHST- 2017/08/01 00:00 [revised]
PHST- 2017/09/22 00:00 [accepted]
PHST- 2017/11/12 06:00 [pubmed]
PHST- 2017/12/20 06:00 [medline]
PHST- 2017/11/12 06:00 [entrez]
PHST- 2018/06/04 00:00 [pmc-release]
AID - jem.20170453 [pii]
AID - 20170453 [pii]
AID - 10.1084/jem.20170453 [doi]
PST - ppublish
SO  - J Exp Med. 2017 Dec 4;214(12):3707-3729. doi: 10.1084/jem.20170453. Epub 2017 Nov 
      10.