title: The mechanosensitive APJ internalization via clathrin-mediated endocytosis: A new molecular mechanism of cardiac hypertrophy.
abstract: The G protein-coupled receptor APJ elicits cellular response to diverse extracellular stimulus. Accumulating evidence reveals that APJ receptor plays a prominent role in the cardiomyocyte adapting to hypertrophic stimulation. At present, it remains obscure that the regulatory mechanism of APJ receptor in myocardial hypertrophy. The natural endogenous ligands apelin and Elabela as well as agonists maintain high affinity for the APJ receptor and drive its internalization. Ligand-activated receptor internalization is mainly performed by clathrin-mediated endocytic pathway. Simultaneously, clathrin-mediated endocytosis takes participate in the occurrence and development of cardiac hypertrophy. In this study, we hypothesize that natural ligands and agonists induce the mechanosensitive APJ internalization via clathrin-mediated endocytosis. APJ internalization may contribute to the development of cardiac hypertrophy. The mechanosensitive APJ internalization via clathrin-mediated endocytosis may be a new molecular mechanism of cardiac hypertrophy.
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Lu
authors.initials: L
authors.lastname: He
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Learning Key Laboratory for Pharmacoproteomics, University of South China, Hengyang 421001, China. Electronic address: llanfang6@126.com.
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
mesh_terms: D000073861:Apelin; D000075244:Apelin Receptors; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D002966:Clathrin / Q000502:physiology*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008024:Ligands; D040542:Mechanotransduction, Cellular; D008955:Models, Cardiovascular; D036361:Peptide Hormones / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*
chemical_list: C000601133:APELA protein, human; C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D002966:Clathrin; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled