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

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

Hypertension research : official journal of the Japanese Society of Hypertension 2022 Jan

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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. © 2021. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Citation

Kouichi Tamura, Kengo Azushima, Sho Kinguchi, Hiromichi Wakui, Takahiro Yamaji. ATRAP, a receptor-interacting modulator of kidney physiology, as a novel player in blood pressure and beyond. Hypertension research : official journal of the Japanese Society of Hypertension. 2022 Jan;45(1):32-39