Thekkinghat, AA and Yadav, KK and Rangarajan, PN (2019) Apolipoprotein L9 interacts with LC3/GABARAP and is a microtubule-associated protein with a widespread subcellular distribution. In: Biology Open, 8 (9).
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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.
| Item Type: | Journal Article |
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| Publication: | Biology Open |
| Publisher: | Company of Biologists Ltd |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | apolipoprotein L; apolipoprotein L9; autophagy related protein 8 family; bafilomycin A1; chloroquine; fprl70 protein; gabaa receptor associated protein; gabarapl1 protein; gabarapl2 protein; glutathione transferase; lc3 protein; lc3a protein; lc3b protein; lipid binding protein; lir protein; lysosome associated membrane protein 1; microtubule associated protein; mutant protein; triton x 100; unclassified drug, amino acid sequence; animal cell; Article; autophagosome; cell lysate; cell stress; cellular distribution; controlled study; deletion mutant; human; human cell; in vitro study; lipid transport; lysosome; macroautophagy; membrane binding; mitochondrial membrane; mitochondrion swelling; mitophagy; mouse; nonhuman; oligomerization; protein analysis; protein domain; protein family; protein localization; protein motif; protein protein interaction; selective autophagy |
| Department/Centre: | Division of Biological Sciences > Biochemistry |
| Date Deposited: | 25 Oct 2022 11:48 |
| Last Modified: | 25 Oct 2022 11:48 |
| URI: | https://eprints.iisc.ac.in/id/eprint/77581 |
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