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8.A.80 The Renin Receptor (RR) Family 

The renin receptor functions as a renin and prorenin cellular receptor. It may mediate renin-dependent cellular responses by activating ERK1 and ERK2. By increasing the catalytic efficiency of renin in AGT/angiotensinogen conversion to angiotensin I, it may also play a role in the renin-angiotensin system (Nguyen et al. 2002).

(Pro)renin receptor (PRR) is highly expressed in the distal nephron. Administration of PRO20, a decoy peptide antagonist of PRR, to K+-loaded animals elevated plasma K+ levels and decreased urinary K+ excretion, accompanied by suppressed aldosterone excretion (Xu et al. 2016).  High K+ downregulates Na+-Cl- cotransporter (NCC) expression but upregulated the renal outer medullary K+ channel (ROMK), calcium-activated potassium channel subunit alpha-1 (α-BK), α-Na+-K+-ATPase (α-NKA), and epithelial Na+ channel subunit beta (β-ENaC), all of which were blunted by PRO20. Following HK, urinary but not plasma renin was upregulated, which was blunted by PRO20. The same experiments performed using adrenalectomized (ADX) rats yielded similar results.  Spironolactone treatment in high K+-loaded ADX rats attenuated kaliuresis but promoted natriuresis associated with the suppressed responses of β-ENaC, α-NKA, ROMK, and α-BK protein expression. Thus, renal PRR regulates K+ homeostasis through a local mechanism involving the intrarenal renin-angiotensin-aldosterone system and coordinates the regulation of several membrane Na+ and K+ transporting proteins (Xu et al. 2016).

References associated with 8.A.80 family:

Danser, A.H. (2015). The Role of the (Pro)renin Receptor in Hypertensive Disease. Am J Hypertens 28: 1187-1196. 25890829
Guida, M.C., T. Hermle, L.A. Graham, V. Hauser, M. Ryan, T.H. Stevens, and M. Simons. (2018). ATP6AP2 functions as a V-ATPase assembly factor in the endoplasmic reticulum. Mol. Biol. Cell mbcE18040234. [Epub: Ahead of Print] 29995586
Ichihara, A. and M.S. Yatabe. (2019). The (pro)renin receptor in health and disease. Nat Rev Nephrol 15: 693-712. 31164719
Kanda, A. (2015). [Atp6ap2/ (Pro) renin Receptor is Required for Laminar Formation during Retinal Development in Mice]. Nippon Ganka Gakkai Zasshi 119: 787-798. 26685483
Nguyen, G., F. Delarue, C. Burcklé, L. Bouzhir, T. Giller, and J.D. Sraer. (2002). Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest 109: 1417-1427. 12045255
Wanka, H., P. Lutze, D. Staar, B. Peters, A. Morch, L. Vogel, R.K. Chilukoti, G. Homuth, J. Sczodrok, I. Bäumgen, and J. Peters. (2017). (Pro)renin receptor (ATP6AP2) depletion arrests As4.1 cells in the G0/G1 phase thereby increasing formation of primary cilia. J Cell Mol Med 21: 1394-1410. 28215051
Xu, C., A. Lu, H. Wang, H. Fang, L. Zhou, P. Sun, and T. Yang. (2016). (Pro)Renin Receptor Regulates Potassium Homeostasis through a Local Mechanism. Am. J. Physiol. Renal Physiol ajprenal.00043.2016. [Epub: Ahead of Print] 27440776
Zima, V., K. Šebková, K. Šimečková, T. Dvořák, V. Saudek, and M. Kostrouchová. (2015). Prorenin Receptor Homologue VHA-20 is Critical for Intestinal pH Regulation, Ion and Water Management and Larval Development in C. elegans. Folia Biol (Praha) 61: 168-177. 26667573