Kidney-disease-associated variants of Apolipoprotein L1 show gain of function in cation channel activity.

ABSTRACT: Variants in Apolipoprotein L1 (ApoL1) are known to be responsible for increased risk of some progressive kidney diseases among people of African ancestry. ApoL1 is an amphitropic protein that can insert into phospholipid membranes and confer anion- or cation-selective permeability to phospholipid membranes depending on pH. Whether these activities differ among the variants or whether they contribute to disease pathogenesis is unknown. We used assays of voltage-driven ion flux from phospholipid vesicles and of stable membrane association to assess differences among ApoL1 isoforms. There is a significant (approximately twofold) increase in the cation-selective ion permease activity of the two kidney-disease-associated variants compared with the reference protein. In contrast, we find no diff

SUBMITTER: Bruno J 

PROVIDER: S-EPMC7948812 | biostudies-literature | 2021 Jan-Jun

REPOSITORIES: biostudies-literature