Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2

被引：279

作者：

Kornak, Uwe ^{[1
,2
]}

Reynders, Ellen ^{[3
,4
]}

Dimopoulou, Aikaterini ^{[1
,2
]}

van Reeuwijk, Jeroen ^{[5
]}

Fischer, Bjoern ^{[1
,2
]}

Rajab, Anna ^{[6
]}

Budde, Birgit ^{[7
,8
]}

Nurnberg, Peter ^{[7
,8
]}

Foulquier, Francois ^{[9
]}

Lefeber, Dirk ^{[10
]}

Urban, Zsolt ^{[11
,12
]}

Gruenewald, Stephanie ^{[13
]}

Annaert, Wim ^{[3
,4
]}

Brunner, Han G. ^{[5
]}

van Bokhoven, Hans ^{[5
]}

Wevers, Ron ^{[10
]}

Morava, Eva ^{[10
]}

Matthijs, Gert ^{[9
]}

Van Maldergem, Lionel ^{[14
]}

Mundlos, Stefan ^{[1
,2
,9
]}

机构：

[1] Charite Univ Med Berlin, Inst Med Genet, Berlin, Germany

[2] Max Planck Inst Mol Genet, Berlin, Germany

[3] Katholieke Univ Leuven, Ctr Human Genet, Lab Membrane Trafficking, B-3000 Louvain, Belgium

[4] Katholieke Univ Leuven VIB, Dept Mol & Dev Genet, B-3000 Louvain, Belgium

[5] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, NL-3525 GA Nijmegen, Netherlands

[6] Minist Hlth, Directorate Gen Hlth Affairs, Genet Unit, Muscat 113, Oman

[7] Univ Cologne, CCG, D-50674 Cologne, Germany

[8] Univ Cologne, Inst Genet, D-50674 Cologne, Germany

[9] Katholieke Univ Leuven, Ctr Human Genet, Lab Mol Diagnost, B-3000 Louvain, Belgium

[10] Univ Med Ctr Nijmegen, Lab Peiat & Neurol, Dept Pediat, NL-6525 GA Nijmegen, Netherlands

[11] Washington Univ, Dept Pediat, St Louis, MO 63110 USA

[12] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[13] Great Ormond St Hosp Children Trust NHS, London WC1N 3JH, England

[14] Univ Liege, CHU Sart Tilman, Ctr Genet Humaine, B-4000 Liege, Belgium

来源：

NATURE GENETICS | 2008年 / 40卷 / 01期

关键词：

D O I：

10.1038/ng.2007.45

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We identified loss-of-function mutations in ATP6V0A2, encoding the a2 subunit of the V-type H+ ATPase, in several families with autosomal recessive cutis laxa type II or wrinkly skin syndrome. The mutations result in abnormal glycosylation of serum proteins (CDG-II) and cause an impairment of Golgi trafficking in fibroblasts from affected individuals. These results indicate that the a2 subunit of the proton pump has an important role in Golgi function.

引用

页码：32 / 34

页数：3

共 15 条

[1] Neutralization of pH in the Golgi apparatus causes redistribution of glycosyltransferases and changes in the O-glycosylation of mucins [J].

Axelsson, MAB ;

Karlsson, NG ;

Steel, DM ;

Ouwendijk, J ;

Nilsson, T ;

Hansson, GC .

GLYCOBIOLOGY, 2001, 11 (08) :633-644

[2] Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II [J].

Foulquier, F ;

Vasile, E ;

Schollen, E ;

Callewaert, N ;

Raemaekers, T ;

Quelhas, D ;

Jaeken, J ;

Mills, P ;

Winchester, B ;

Krieger, M ;

Annaert, W ;

Matthijs, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (10) :3764-3769

[3] A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical role for the Cog1-Cog8 interaction in COG complex formation [J].

Foulquier, Francois ;

Ungar, Daniel ;

Reynders, Ellen ;

Zeevaert, Renate ;

Mills, Philippa ;

Garcia-Silva, Maria Teresa ;

Briones, Paz ;

Winchester, Bryan ;

Morelle, Willy ;

Krieger, Monty ;

Annaert, Willem ;

Matthijs, Gert .

HUMAN MOLECULAR GENETICS, 2007, 16 (07) :717-730

[4] Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis [J].

Frattini, A ;

Orchard, PJ ;

Sobacchi, C ;

Giliani, S ;

Abinun, M ;

Mattsson, JP ;

Keeling, DJ ;

Andersson, AK ;

Wallbrandt, P ;

Zecca, L ;

Notarangelo, LD ;

Vezzoni, P ;

Villa, A .

NATURE GENETICS, 2000, 25 (03) :343-346

[5]

Freeze HH, 2006, NAT REV GENET, V7, P537, DOI 10.1038/nrg1894

[6] Quantitative proteomics analysis of the secretory pathway [J].

Gilchrist, Annalyn ;

Au, Catherine E. ;

Hiding, Johan ;

Bell, Alexander W. ;

Fernandez-Rodriguez, Julia ;

Lesimple, Souad ;

Nagaya, Hisao ;

Roy, Line ;

Gosline, Sara J. C. ;

Hallett, Michael ;

Paiement, Jacques ;

Kearney, Robert E. ;

Nilsson, Tommy ;

Bergeron, John J. M. .

CELL, 2006, 127 (06) :1265-1281

[7] V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway [J].

Hurtado-Lorenzo, A ;

Skinner, M ;

El Annan, J ;

Futai, M ;

Sun-Wada, GH ;

Bourgoin, S ;

Casanova, J ;

Wildeman, A ;

Bechoua, S ;

Ausiello, DA ;

Brown, D ;

Marshansky, V .

NATURE CELL BIOLOGY, 2006, 8 (02) :124-U8

[8] Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins [J].

Miesenböck, G ;

De Angelis, DA ;

Rothman, JE .

NATURE, 1998, 394 (6689) :192-195

[9] Defective protein glycosylation in patients with cutis laxa syndrome [J].

Morava, E ;

Wopereis, S ;

Coucke, P ;

Gillessen-Kaesbach, G ;

Voit, T ;

Smeitink, J ;

Wevers, R ;

Grünewald, S .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2005, 13 (04) :414-421

[10]

MORAVA E, IN PRESS EUR J HUM G

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