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 b

SUBMITTER: Rujano MA 

PROVIDER: S-EPMC5716037 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature