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The mechanisms behind decreased internalization of angiotensin II type 1 receptor

Jingwei Bian1, Suli Zhang1, Ming Yi1

  • 1Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Vascular Pharmacology
|February 10, 2018
PubMed

Insights

Reduced internalization of angiotensin II type 1 receptor (AT1R) contributes to cardiovascular diseases. This review details mechanisms affecting AT1R internalization, including agonist binding, phosphorylation, endocytosis, and recycling.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cell Biology
  • Pharmacology

Background:

  • Angiotensin II type 1 receptor (AT1R) internalization is crucial for cardiovascular homeostasis.
  • Reduced AT1R internalization is linked to cardiovascular diseases like hypertension.
  • Mechanisms underlying decreased AT1R internalization remain incompletely understood.

Purpose of the Study:

  • To review the key steps in AT1R internalization.
  • To summarize potential mechanisms reducing AT1R internalization.
  • To provide insights into AT1R-related cardiovascular pathologies.

Main Methods:

  • Literature review focusing on AT1R internalization pathways.
  • Analysis of factors affecting agonist-receptor binding.
  • Examination of receptor phosphorylation and signaling.
  • Investigation of endocytosis and recycling processes.

Main Results:

  • Reduced AT1R internalization can stem from agonist properties, altered phosphorylation, impaired endocytosis, or enhanced recycling.
  • Specific molecular players like PtdIns(4,5)P2, kinases, Rab4/11, and ARAP1 influence AT1R internalization.
  • Dysregulation of AT1R internalization involves changes in receptor-protein interactions and signaling complex conformation.

Conclusions:

  • Multiple molecular mechanisms can lead to reduced AT1R internalization.
  • Understanding these mechanisms is vital for developing therapies for AT1R-mediated cardiovascular diseases.
  • Further research into AT1R trafficking and signaling is warranted.

Keywords:
AT(1)R-associated proteinAngiotensin II type 1 receptorEndocytosisInternalizationRecycling

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