Cold-sensitive phenotypes of a yeast null mutant of ARV1 support its role as a GPI flippase.

Abstract:

:Glycosylphosphatidylinositol (GPI) is synthesized in the endoplasmic reticulum (ER) and added onto proteins to form GPI-anchored proteins. Among the many proteins involved in this process, ACAT-related enzyme-2 required for viability 1 (Arv1) is a candidate, functioning as a flippase that translocates GPI intermediates from the cytoplasmic side into the luminal side of the ER membranes. Here, we show that the deletion of the ARV1 gene in yeast leads to cold-sensitive defects in cell growth and GPI anchor synthesis. Furthermore, complementation assays show that the overexpression of a missense human ARV1-G189R mutant does not completely restore the cold-sensitive phenotypes of the yeast arv1 mutant. Our results support the proposed role of Arv1 in GPI anchor synthesis and suggest that ARV1-linked human diseases result from defective GPI anchor synthesis.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Okai H,Ikema R,Nakamura H,Kato M,Araki M,Mizuno A,Ikeda A,Renbaum P,Segel R,Funato K

doi

10.1002/1873-3468.13843

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

2431-2439

issue

15

eissn

0014-5793

issn

1873-3468

journal_volume

594

pub_type

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