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Angiotensin II Type 1 Receptor Binding Molecule ATRAP as a Possible Modulator of Renal Sodium Handling and Blood

K Tamura1, H Wakui, K Azushima

  • 1Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. tamukou@med.yokohama-cu.ac.jp.

Current Medicinal Chemistry
|August 22, 2015
PubMed

Insights

ATRAP, a novel protein, regulates angiotensin II type 1 receptor (AT1R) signaling. It promotes receptor internalization and inhibits pathological responses, offering a potential therapeutic target for hypertension and organ damage.

Area of Science:

  • Cardiovascular Research
  • Renal Physiology
  • Endocrinology

Background:

  • Renin-angiotensin system (RAS) overactivation via angiotensin II type 1 receptor (AT1R) signaling causes hypertension and organ damage.
  • Physiological AT1R signaling is crucial for normal kidney development and maintaining cardiovascular/renal homeostasis.
  • The dual role of AT1R necessitates selective modulation strategies for therapeutic benefit.

Purpose of the Study:

  • To identify novel molecules that selectively modulate AT1R signaling.
  • To investigate the functional role of a newly identified protein, ATRAP, in AT1R signaling and related pathophysiology.

Main Methods:

  • Yeast two-hybrid screening of a mouse kidney cDNA library to identify AT1R-interacting proteins.
  • Functional analysis of ATRAP in cultured cells and mouse models.
  • Assessment of ATRAP expression in various tissues, particularly the kidney.
  • Utilizing genetically engineered mice with modified ATRAP expression to study its in vivo effects.

Main Results:

  • ATRAP was identified as a direct interactor of the AT1R carboxyl-terminal cytoplasmic domain.
  • ATRAP promotes constitutive AT1R internalization in cultured cells.
  • ATRAP inhibits Ang II-mediated pathological responses in mouse renal cells.
  • Genetic modification of ATRAP influenced renal sodium handling and blood pressure regulation in response to pathological stimuli.

Conclusions:

  • ATRAP plays a significant role in regulating AT1R signaling.
  • ATRAP's ability to inhibit pathological Ang II effects suggests its therapeutic potential.
  • ATRAP is a promising target for developing new strategies to manage hypertension and related organ damage.

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