PUBLICATION
Molecular determinants on extracellular loop domains that dictate interaction between β-arrestin and human APJ receptor
- Authors
- Ashokan, A., Kameswaran, M., Aradhyam, G.K.
- ID
- ZDB-PUB-200516-14
- Date
- 2019
- Source
- FEBS letters 593: 634-643 (Journal)
- Registered Authors
- Keywords
- APJ receptor, Akt phosphorylation, apelin, cell migration, β-arrestin
- MeSH Terms
-
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Apelin/genetics*
- Apelin/metabolism
- Apelin Receptors/chemistry*
- Apelin Receptors/genetics
- Apelin Receptors/metabolism
- Cell Movement
- Chickens/genetics
- Chickens/metabolism
- HEK293 Cells
- Humans
- Iodine Radioisotopes
- Mutation
- Perciformes/genetics
- Perciformes/metabolism
- Protein Interaction Domains and Motifs
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism
- Recombinant Fusion Proteins/genetics
- Recombinant Fusion Proteins/metabolism
- Salmo salar/genetics
- Salmo salar/metabolism
- Sequence Alignment
- Sequence Homology, Amino Acid
- Signal Transduction*
- Staining and Labeling/methods
- Xenopus laevis/genetics
- Xenopus laevis/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- beta-Arrestins/chemistry*
- beta-Arrestins/genetics
- beta-Arrestins/metabolism
- PubMed
- 30801688 Full text @ FEBS Lett.
Citation
Ashokan, A., Kameswaran, M., Aradhyam, G.K. (2019) Molecular determinants on extracellular loop domains that dictate interaction between β-arrestin and human APJ receptor. FEBS letters. 593:634-643.
Abstract
The human APJ receptor (APJR), activated by apelin isoforms, regulates cardiovascular functions and fluid homeostasis. Understanding its structure-function relationship is crucial for a comprehensive knowledge of signalling aberrations that cause several physiological disorders. Here, we demonstrate the influence of extracellular loop (ECL) domains in the mechanism of β-arrestin-mediated signalling from human APJR: Apelin system. Alanine mutations of evolutionarily conserved residues were characterized using receptor internalization, β-arrestin pull-down, Akt phosphorylation and cell migration assay. C281A and 268 KTL270 -AAA in ECL3 were deficient in all assays, whereas 183 MDYS186 -AAAA mutant in ECL2 showed impaired β-arrestin-mediated signalling but demonstrated Gi -dependent cell migration. Our findings establish that conserved residues in the extracellular domain play a prominent role in modulating receptor interactions with the β-arrestin signalling cascade.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping