Docosahexaenoic acid-containing phosphatidic acid interacts with clathrin coat assembly protein AP180 and regulates its interaction with clathrin

Autor: Fumio Sakane, Fumi Hoshino
Rok vydání: 2022
Předmět:
WT
wild type
Diacylglycerol kinase
PG
phosphatidylglycerol
Biochemistry
GST
glutathione S-transferase
WB
Western blotting
PC
phosphatidylcholine
Mice
chemistry.chemical_compound
Phosphatidic acid
AP180
PA
phosphatidic acid
Receptor
Internalization
media_common
PI(4
5)P2
phosphatidylinositol 4
5-bisphosphate
biology
Chol
cholesterol
Brain
PS
phosphatidylserine
Clathrin-mediated endocytosis
Endocytosis
Recombinant Proteins
Cell biology
Docosahexaenoic acid
DGK
diacylglycerol kinase
Monomeric Clathrin Assembly Proteins
Phosphatidylinositol 4
5-bisphosphate
AD
Alzheimer's disease
Protein Binding
CL
cardiolipin
Docosahexaenoic Acids
media_common.quotation_subject
Biophysics
Phosphatidic Acids
CME
clathrin-mediated endocytosis
PE
phosphatidylethanolamine
Clathrin
Article
PI
phosphatidylinositol
Cell Line
CID
C-terminal intrinsically disordered region
Animals
Humans
Protein Interaction Domains and Motifs
Phosphatidylinositol
PLD
phospholipase D
Molecular Biology
Binding Sites
CHC
clathrin heavy chain
Host Microbial Interactions
SARS-CoV-2
COVID-19
Cell Biology
Virus Internalization
CBB
Coomassie Brilliant Blue
chemistry
Clathrin coat assembly protein AP180
biology.protein
Ap180
ANTH
AP180 N-terminal homology domain
Zdroj: Biochemical and Biophysical Research Communications
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2021.11.097
Popis: 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 (18:0/22:6-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 18:0/22:6-PA, and a lysine-rich motif (K38–K39–K40) was essential for binding. The 18:0/22:6-PA in liposomes in 100 nm diameter showed strong AP180-binding activity at neutral pH. Notably, 18:0/22:6-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 18:0/22:6-PA selectively regulates the disassembly of AP180/clathrin-containing cages.
Graphical abstract Image 1
Databáze: OpenAIRE
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