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Identification of the GABARAP binding determinant in PI4K2A.
- Source :
-
Bioscience reports [Biosci Rep] 2024 Oct 30; Vol. 44 (10). - Publication Year :
- 2024
-
Abstract
- GABARAP is a member of the ATG8 family of ubiquitin-like autophagy related proteins. It was initially discovered as a facilitator of GABA-A receptor translocation to the plasma membrane and has since been shown to promote the intracellular transport of a variety of other proteins under non-autophagic conditions. We and others have shown that GABARAP interacts with the Type II phosphatidylinositol 4-kinase, PI4K2A, and that this interaction is important for autophagosome-lysosome fusion. Here, we identify a 7-amino acid segment within the PI4K2A catalytic domain that contains the GABARAP interaction motif (GIM). This segment resides in an exposed loop that is not conserved in the other mammalian Type II PI 4-kinase, PI4K2B, explaining the specificity of GABARAP binding to the PI4K2A isoform. Mutation of the PI4K2A GIM inhibits GABARAP binding and PI4K2A-mediated recruitment of cytosolic GABARAP to subcellular organelles. We further show that GABARAP binds to mono-phosphorylated phosphoinositides, PI3P, PI4P, and PI5P, raising the possibility that these lipids contribute to the binding energies that drive GABARAP-protein interactions on membranes.<br /> (© 2024 The Author(s).)
- Subjects :
- Humans
HEK293 Cells
Animals
Catalytic Domain
Autophagy
Phosphorylation
Phosphatidylinositols metabolism
Minor Histocompatibility Antigens
Phosphotransferases (Alcohol Group Acceptor)
Apoptosis Regulatory Proteins metabolism
Apoptosis Regulatory Proteins genetics
Microtubule-Associated Proteins metabolism
Microtubule-Associated Proteins genetics
Adaptor Proteins, Signal Transducing metabolism
Adaptor Proteins, Signal Transducing genetics
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4935
- Volume :
- 44
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Bioscience reports
- Publication Type :
- Academic Journal
- Accession number :
- 39344512
- Full Text :
- https://doi.org/10.1042/BSR20240200