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Biol Open. 2019 Sep 25;8(9). pii: bio045930. doi: 10.1242/bio.045930.

Apolipoprotein L9 interacts with LC3/GABARAP and is a microtubule-associated protein with a widespread subcellular distribution.

Author information

1
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India arvinda@iisc.ac.in pnr@iisc.ac.in.
2
Department of Biochemistry, Indian Institute of Science, Bangalore, 560012, India.

Abstract

Mouse Apolipoprotein L9 is a 34-kDa phosphatidylethanolamine (PE)-binding protein. The gene is present only in mouse and rat genomes; hence it is restricted to two species. To understand why, it is essential to uncover details about its functions in cellular processes. Here we show that ApoL9 interacts with the proteins of the LC3 and GABARAP subfamilies, which are key players in macroautophagy. In vitro binding studies show a strong association with GABARAP, and in amino acid-starved cells it preferentially interacts with lipidated LC3B, likely by binding to its PE moiety through its lipid-binding domain. On treatment with autophagy inhibitors bafilomycin A1 and chloroquine, ApoL9 is found near swollen mitochondria and on lysosomes/LAMP1-positive compartments. However, ApoL9 itself does not seem to be degraded as a result of autophagy, suggesting that it is not an autophagy cargo receptor. Deletions in a putative transmembrane region between amino acids 110 and 145 abolish binding to PE. In addition, ApoL9 can redistribute to stress granules, can homo-oligomerize, and is a microtubule-associated protein. In short, its distribution in the cell is quite widespread, suggesting that it could have functions at the intersection of membrane binding and reorganization, autophagy, cellular stress and intracellular lipid transport.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

Autophagy adaptor; Extracellular mitochondria; Lipid-binding protein; Lipidated LC3; Lysosomal localization; Phosphatidylethanolamine-binding

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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