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.
Artículo
en Inglés
| 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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Ácidos Fosfatidicos
/
Ácidos Docosahexaenoicos
/
Clatrina
/
Proteínas de Ensamble de Clatrina Monoméricas
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Biochem Biophys Res Commun
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
J.bbrc.2021.11.097
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