Vacuolar H+-ATPase meets glycosylation in patients with cutis laxa

Mailys Guillard, Aikaterini Dimopoulou, Björn Fischer, Eva Morava-Kozicz, Dirk J. Lefeber, Uwe Kornak, Ron A. Wevers

Research output: Contribution to journalReview article

36 Scopus citations

Abstract

Glycosylation of proteins is one of the most important post-translational modifications. Defects in the glycan biosynthesis result in congenital malformation syndromes, also known as congenital disorders of glycosylation (CDG). Based on the iso-electric focusing patterns of plasma transferrin and apolipoprotein C-III a combined defect in N- and O-glycosylation was identified in patients with autosomal recessive cutis laxa type II (ARCL II). Disease-causing mutations were identified in the ATP6V0A2 gene, encoding the a2 subunit of the vacuolar H+-ATPase (V-ATPase). The V-ATPases are multi-subunit, ATP-dependent proton pumps located in membranes of cells and organels. In this article, we describe the structure, function and regulation of the V-ATPase and the phenotypes currently known to result from V-ATPase mutations. A clinical overview of cutis laxa syndromes is presented with a focus on ARCL II. Finally, the relationship between ATP6V0A2 mutations, the glycosylation defect and the ARCLII phenotype is discussed.

Original languageEnglish (US)
Pages (from-to)903-914
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1792
Issue number9
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

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Keywords

  • Apolipoprotein C III
  • Congenital disorders of glycosylation
  • Cutis laxa
  • Glycosylation
  • OMIM 219200
  • V-ATPase

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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