Dataset Information

Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization.

ABSTRACT: Kidney fibrosis is a common pathway that leads to chronic kidney disease. Angiotensin II type-1 receptor (AT1R)-associated protein (ATRAP) was originally identified as an AT1R-binding protein. Previously, we reported that systemic knockout of ATRAP exacerbates kidney fibrosis in aged mice. Although these effects of ATRAP appeared to be AT1R-independent actions, the molecular mechanism remains poorly understood. To elucidate the molecular mechanism of ATRAP independent of AT1R, we explored novel ATRAP-interacting proteins. Mass spectrometric analysis of the immunoprecipitants of a Flag-tagged ATRAP complex revealed 376 candidate proteins that potentially interact with ATRAP. Gene ontology analysis revealed that proteins related to vesicle trafficking, membrane transport, and many membrane proteins, including transferrin receptor 1 (TfR1), were enriched. Because TfR1 promotes cellular iron uptake and iron is a key factor involved in kidney fibrosis, we focused on TfR1 and confirmed that it interacts with ATRAP. In addition, our findings revealed that enhanced ATRAP expression decreased cell-surface TfR1 expression without altering the overall cellular TfR1 expression levels. Furthermore, enhanced ATRAP expression attenuated cellular iron levels. Together, our results highlight the role of ATRAP as a suppressor of TfR1 that functions by facilitating TfR1 internalization, which affects iron metabolism and oxidative stress signaling.

SUBMITTER: Abe E

PROVIDER: S-EPMC9576747 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization.

Abe Eriko E Yamashita Akio A Hirota Keigo K Yamaji Takahiro T Azushima Kengo K Urate Shingo S Suzuki Toru T Tanaka Shohei S Taguchi Shinya S Tsukamoto Shunichiro S Uehara Tatsuki T Wakui Hiromichi H Tamura Kouichi K Takahashi Hidehisa H

Scientific reports 20221017 1

Kidney fibrosis is a common pathway that leads to chronic kidney disease. Angiotensin II type-1 receptor (AT1R)-associated protein (ATRAP) was originally identified as an AT1R-binding protein. Previously, we reported that systemic knockout of ATRAP exacerbates kidney fibrosis in aged mice. Although these effects of ATRAP appeared to be AT1R-independent actions, the molecular mechanism remains poorly understood. To elucidate the molecular mechanism of ATRAP independent of AT1R, we explored novel ...[more]

PMID: 36253401

Similar Datasets

Project description:The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin-angiotensin system (RAS) in favor of the ACE-angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II-AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.

Dataset Information

Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization.

Publications

Angiotensin II type-1 receptor-associated protein interacts with transferrin receptor-1 and promotes its internalization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets