Docosahexaenoic acid-containing phosphatidic acid interacts with clathrin coat assembly protein AP180 and regulates its interaction with clathrin.
Biochem Biophys Res Commun
; 587: 69-77, 2022 01 08.
Article
in English
| MEDLINE | ID: covidwho-1540389
ABSTRACT
The clathrin coat assembly protein AP180 drives endocytosis, which is crucial for numerous physiological events, such as the internalization and recycling of receptors, uptake of neurotransmitters and entry of viruses, including SARS-CoV-2, by interacting with clathrin. Moreover, dysfunction of AP180 underlies the pathogenesis of Alzheimer's disease. Therefore, it is important to understand the mechanisms of assembly and, especially, disassembly of AP180/clathrin-containing cages. Here, we identified AP180 as a novel phosphatidic acid (PA)-binding protein from the mouse brain. Intriguingly, liposome binding assays using various phospholipids and PA species revealed that AP180 most strongly bound to 1-stearoyl-2-docosahexaenoyl-PA (180/226-PA) to a comparable extent as phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), which is known to associate with AP180. An AP180 N-terminal homology domain (1-289 aa) interacted with 180/226-PA, and a lysine-rich motif (K38-K39-K40) was essential for binding. The 180/226-PA in liposomes in 100 nm diameter showed strong AP180-binding activity at neutral pH. Notably, 180/226-PA significantly attenuated the interaction of AP180 with clathrin. However, PI(4,5)P2 did not show such an effect. Taken together, these results indicate the novel mechanism by which 180/226-PA selectively regulates the disassembly of AP180/clathrin-containing cages.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Phosphatidic Acids
/
Docosahexaenoic Acids
/
Clathrin
/
Monomeric Clathrin Assembly Proteins
Limits:
Animals
/
Humans
Language:
English
Journal:
Biochem Biophys Res Commun
Year:
2022
Document Type:
Article
Affiliation country:
J.bbrc.2021.11.097
Similar
MEDLINE
...
LILACS
LIS