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  • Review Article
  • Review Series - Basic Science in Hypertension Research
  • Published:

ATRAP, a receptor-interacting modulator of kidney physiology, as a novel player in blood pressure and beyond

Hypertension Research volume 45, pages 32–39 (2022)Cite this article

Abstract

Pathological activation of kidney angiotensin II (Ang II) type 1 receptor (AT1R) signaling stimulates tubular sodium transporters, including epithelial sodium channels, to increase sodium reabsorption and blood pressure. During a search for a means to functionally and selectively modulate AT1R signaling, a molecule directly interacting with the carboxyl-terminal cytoplasmic domain of AT1R was identified and named AT1R-associated protein (ATRAP/Agtrap). We showed that ATRAP promotes constitutive AT1R internalization to inhibit pathological AT1R activation in response to certain stimuli. In the kidney, ATRAP is abundantly distributed in epithelial cells along the proximal and distal tubules. Results from genetically engineered mice with modified ATRAP expression show that ATRAP plays a key role in the regulation of renal sodium handling and the modulation of blood pressure in response to pathological stimuli and further suggest that the function of kidney tubule ATRAP may be different between distal tubules and proximal tubules, implying that ATRAP is a target of interest in hypertension.

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Acknowledgements

The authors were supported by grants from Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science, Uehara Memorial Foundation, and Salt Science Research Foundation (18C4, 19C4, 20C4). The authors were also supported by the Yokohama City University research grant “KAMOME Project”, Japan Agency for Medical Research and Development (AMED), and by the Translational Research program Strategic PRomotion for practical application of INnovative medical Technology (TR-SPRINT) from AMED.

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  1. Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Kouichi Tamura, Kengo Azushima, Sho Kinguchi, Hiromichi Wakui & Takahiro Yamaji

  2. Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore

    Takahiro Yamaji

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Tamura, K., Azushima, K., Kinguchi, S. et al. ATRAP, a receptor-interacting modulator of kidney physiology, as a novel player in blood pressure and beyond. Hypertens Res 45, 32–39 (2022). https://doi.org/10.1038/s41440-021-00776-1

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