Acknowledgements
We acknowledge support from the National Key Basic Research Program of China (2018YFC1003600 to J. S., Z. X., W. X.), the National Natural Science Foundation of China (81773704 to J. S., 81771001 to Z. X., 81901548 to D. Z.); the Shandong Provincial Natural Science Foundation (ZR2019BC078 to D. Z.); the Shandong Provincial Medicine and Health Science Technology Development Program (2017WS692 to D. Z.); the National Science Fund for Distinguished Young Scholars (81825022 to J. S.), the Fundamental Research Funds of Shandong University (2018JC025 to Z. X.) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT13028).
Conflict of Interest: The authors declare no competing interests.
References
Abe K, Takano H, Ito T (1984). Microvasculature of the mouse epididymis, with special reference to fenestrated capillaries localized in the initial segment. The Anatomical record 209 (2): 209-218.
Abou-Haila A, Fain-Maurel MA (1984). Regional differences of the proximal part of mouse epididymis: morphological and histochemical characterization. The Anatomical record 209 (2): 197-208.
Aitken RJ (2006). Sperm function tests and fertility. International journal of andrology29 (1): 69-75; discussion 105-108.
Aitken RJ, Nixon B, Lin M, Koppers AJ, Lee YH, Baker MA (2007). Proteomic changes in mammalian spermatozoa during epididymal maturation. Asian journal of andrology9 (4): 554-564.
Arkoun B, Gautier C, Delalande C, Barrier-Battut I, Guenon I, Goux D, et al. (2014). Stallion spermatozoa: putative target of estrogens; presence of the estrogen receptors ESR1, ESR2 and identification of the estrogen-membrane receptor GPER. General and comparative endocrinology200: 35-43.
Barrett-Jolley R, Comtois A, Davies NW, Stanfield PR, Standen NB (1996). Effect of adenosine and intracellular GTP on KATP channels of mammalian skeletal muscle.The Journal of membrane biology 152 (2):111-116.
Bennion DM, Steckelings UM, Sumners C (2018). Neuroprotection via AT2 receptor agonists in ischemic stroke.Clin Sci (Lond) 132 (10): 1055-1067.
Bologa CG, Revankar CM, Young SM, Edwards BS, Arterburn JB, Kiselyov AS, et al. (2006). Virtual and biomolecular screening converge on a selective agonist for GPR30.Nature chemical biology 2 (4): 207-212.
Brownhill VR, Hourani SM, Kitchen I (1996). Differential distribution of adenosine A2 receptors in the epididymal and prostatic portions of the rat vas deferens.European journal of pharmacology 303 (1-2):87-90.
Burkett BN, Schulte BA, Spicer SS (1987). Histochemical evaluation of glycoconjugates in the male reproductive tract with lectin-horseradish peroxidase conjugates: I. Staining of principal cells and spermatozoa in the mouse. The American journal of anatomy 178 (1): 11-22.
Cao X, Huang J, Zhang G, Zuo W, Lan C, Sun Q, et al. (2017). Functional expression of G protein-coupled receptor 30 in immature rat epididymal epithelium.Cell biology international 41 (2): 134-146.
Carmon KS, Gong X, Lin Q, Thomas A, Liu Q (2011). R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/beta-catenin signaling. Proceedings of the National Academy of Sciences of the United States of America108 (28): 11452-11457.
Cassault-Meyer E, Gress S, Seralini GE, Galeraud-Denis I (2014). An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality.Environmental toxicology and pharmacology38 (1): 131-140.
Chevrier C, Dacheux JL (1992). Evolution of the flagellar waveform of ram spermatozoa in relation to the degree of epididymal maturation. Cell motility and the cytoskeleton 23 (1): 8-18.
Clulow J, Jones RC, Hansen LA, Man SY (1998). Fluid and electrolyte reabsorption in the ductuli efferentes testis. Journal of reproduction and fertility. Supplement53: 1-14.
Cornwall GA (2009). New insights into epididymal biology and function. Human reproduction update15 (2): 213-227.
Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, et al. (2004). Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility. Molecular and cellular biology24 (19): 8642-8648.
de Lau W, Barker N, Low TY, Koo BK, Li VS, Teunissen H, et al. (2011). Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling. Nature476 (7360): 293-297.
Demberg LM, Rothemund S, Schoneberg T, Liebscher I (2015). Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2. Biochemical and biophysical research communications 464 (3):743-747.
Deng C, Reddy P, Cheng Y, Luo CW, Hsiao CL, Hsueh AJ (2013). Multi-functional norrin is a ligand for the LGR4 receptor. Journal of cell science 126 (Pt 9): 2060-2068.
Dennis MK, Burai R, Ramesh C, Petrie WK, Alcon SN, Nayak TK, et al. (2009). In vivo effects of a GPR30 antagonist. Nature chemical biology 5 (6):421-427.
Dennis MK, Field AS, Burai R, Ramesh C, Petrie WK, Bologa CG, et al. (2011). Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity. The Journal of steroid biochemistry and molecular biology 127 (3-5): 358-366.
Desimine VL, McCrink KA, Parker BM, Wertz SL, Maning J, Lymperopoulos A (2018). Biased Agonism/Antagonism of Cardiovascular GPCRs for Heart Failure Therapy. International review of cell and molecular biology 339: 41-61.
Dong JH, Wang YJ, Cui M, Wang XJ, Zheng WS, Ma ML, et al. (2017). Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and beta-Arrestin-1-Regulated Lactate Metabolism. Biological psychiatry 81 (8): 654-670.
Elzanaty S, Richthoff J, Malm J, Giwercman A (2002). The impact of epididymal and accessory sex gland function on sperm motility. Hum Reprod 17 (11):2904-2911.
Esther CR, Jr., Howard TE, Marino EM, Goddard JM, Capecchi MR, Bernstein KE (1996). Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Laboratory investigation; a journal of technical methods and pathology 74 (5): 953-965.
Flock T, Hauser AS, Lund N, Gloriam DE, Balaji S, Babu MM (2017). Selectivity determinants of GPCR-G-protein binding. Nature 545 (7654): 317-322.
Flock T, Ravarani CNJ, Sun D, Venkatakrishnan AJ, Kayikci M, Tate CG, et al. (2015). Universal allosteric mechanism for Galpha activation by GPCRs. Nature524 (7564): 173-179.
Folts CJ, Giera S, Li T, Piao X (2019). Adhesion G Protein-Coupled Receptors as Drug Targets for Neurological Diseases. Trends in pharmacological sciences40 (4): 278-293.
Fredholm BB, Abbracchio MP, Burnstock G, Daly JW, Harden TK, Jacobson KA, et al. (1994). Nomenclature and classification of purinoceptors. Pharmacological reviews46 (2): 143-156.
Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB (2003). The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Molecular pharmacology 63 (6):1256-1272.
Funakoshi T, Yanai A, Shinoda K, Kawano MM, Mizukami Y (2006). G protein-coupled receptor 30 is an estrogen receptor in the plasma membrane. Biochemical and biophysical research communications 346 (3): 904-910.
Furness SGB, Liang YL, Nowell CJ, Halls ML, Wookey PJ, Dal Maso E, et al. (2016). Ligand-Dependent Modulation of G Protein Conformation Alters Drug Efficacy. Cell167 (3): 739-749 e711.
Gao Y, Kitagawa K, Shimada M, Uchida C, Hattori T, Oda T, et al. (2006). Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor. [Hokkaido igaku zasshi] The Hokkaido journal of medical science 81 (2): 101-105, 107, 109.
Gautier C, Barrier-Battut I, Guenon I, Goux D, Delalande C, Bouraima-Lelong H (2016). Implication of the estrogen receptors GPER, ESR1, ESR2 in post-testicular maturations of equine spermatozoa. General and comparative endocrinology233: 100-108.
Geldenhuys WJ, Hanif A, Yun J, Nayeem MA (2017). Exploring Adenosine Receptor Ligands: Potential Role in the Treatment of Cardiovascular Diseases. Molecules 22 (6).
Glinka A, Dolde C, Kirsch N, Huang YL, Kazanskaya O, Ingelfinger D, et al. (2011). LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling.EMBO reports 12 (10): 1055-1061.
Gottwald U, Davies B, Fritsch M, Habenicht UF (2006). New approaches for male fertility control: HE6 as an example of a putative target. Molecular and cellular endocrinology 250 (1-2): 49-57.
Guimond MO, Hallberg M, Gallo-Payet N, Wallinder C (2014). Saralasin and Sarile Are AT2 Receptor Agonists.ACS medicinal chemistry letters 5 (10):1129-1132.
Hagaman JR, Moyer JS, Bachman ES, Sibony M, Magyar PL, Welch JE, et al. (1998). Angiotensin-converting enzyme and male fertility. Proceedings of the National Academy of Sciences of the United States of America95 (5): 2552-2557.
Hallberg M, Sumners C, Steckelings UM, Hallberg A (2018). Small-molecule AT2 receptor agonists.Medicinal research reviews 38 (2): 602-624.
Hamann J, Aust G, Arac D, Engel FB, Formstone C, Fredriksson R, et al. (2015). International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacological reviews 67 (2):338-367.
Hara MR, Kovacs JJ, Whalen EJ, Rajagopal S, Strachan RT, Grant W, et al. (2011). A stress response pathway regulates DNA damage through beta2-adrenoreceptors and beta-arrestin-1. Nature 477 (7364): 349-353.
Hauser AS, Attwood MM, Rask-Andersen M, Schioth HB, Gloriam DE (2017). Trends in GPCR drug discovery: new agents, targets and indications. Nature reviews. Drug discovery16 (12): 829-842.
Hauser AS, Chavali S, Masuho I, Jahn LJ, Martemyanov KA, Gloriam DE, et al. (2018). Pharmacogenomics of GPCR Drug Targets. Cell 172 (1-2): 41-54 e19.
Haynes JM (2000). A(2A) adenosine receptor mediated potassium channel activation in rat epididymal smooth muscle. British journal of pharmacology 130 (3):685-691.
Haynes JM, Alexander SP, Hill SJ (1998a). A1 adenosine receptor modulation of electrically-evoked contractions in the bisected vas deferens and cauda epididymis of the guinea-pig. British journal of pharmacology124 (5): 964-970.
Haynes JM, Alexander SP, Hill SJ (1998b). A1 and A2 adenosine receptor modulation of contractility in the cauda epididymis of the guinea-pig. British journal of pharmacology 125 (3): 570-576.
Hermo L, Dworkin J, Oko R (1988). Role of epithelial clear cells of the rat epididymis in the disposal of the contents of cytoplasmic droplets detached from spermatozoa.The American journal of anatomy 183 (2):107-124.
Hess RA (2000). Oestrogen in fluid transport in efferent ducts of the male reproductive tract.Reviews of reproduction 5 (2): 84-92.
Hess RA (2015). Small tubules, surprising discoveries: from efferent ductules in the turkey to the discovery that estrogen receptor alpha is essential for fertility in the male. Animal reproduction 12 (1): 7-23.
Hess RA, Fernandes SA, Gomes GR, Oliveira CA, Lazari MF, Porto CS (2011). Estrogen and its receptors in efferent ductules and epididymis. Journal of andrology32 (6): 600-613.
Hess RA, Nakai M (2000). Histopathology of the male reproductive system induced by the fungicide benomyl. Histology and histopathology 15 (1):207-224.
Homan KT, Tesmer JJ (2014). Structural insights into G protein-coupled receptor kinase function.Current opinion in cell biology 27: 25-31.
Hoshii T, Takeo T, Nakagata N, Takeya M, Araki K, Yamamura K (2007). LGR4 regulates the postnatal development and integrity of male reproductive tracts in mice. Biology of reproduction 76 (2): 303-313.
Hu QX, Dong JH, Du HB, Zhang DL, Ren HZ, Ma ML, et al. (2014). Constitutive Galphai coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein. The Journal of biological chemistry289 (35): 24215-24225.
Isogai S, Deupi X, Opitz C, Heydenreich FM, Tsai CJ, Brueckner F, et al. (2016). Backbone NMR reveals allosteric signal transduction networks in the beta1-adrenergic receptor. Nature 530 (7589): 237-241.
Jackson S, Weingart J, Nduom EK, Harfi TT, George RT, McAreavey D, et al. (2018). The effect of an adenosine A2A agonist on intra-tumoral concentrations of temozolomide in patients with recurrent glioblastoma. Fluids and barriers of the CNS 15 (1): 2.
Jacobson KA, Tosh DK, Jain S, Gao ZG (2019). Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development. Frontiers in cellular neuroscience 13: 124.
Joseph A, Shur BD, Hess RA (2011). Estrogen, efferent ductules, and the epididymis. Biology of reproduction 84 (2): 207-217.
Katleba KD, Legacki EL, Conley AJ, Berger T (2015). Steroid regulation of early postnatal development in the corpus epididymidis of pigs. The Journal of endocrinology225 (3): 125-134.
Khan MJ, Pollock N, Jiang H, Castro C, Nazli R, Ahmed J, et al. (2018). X-linked ADGRG2 mutation and obstructive azoospermia in a large Pakistani family. Scientific reports 8 (1): 16280.
Kim J, Grotegut CA, Wisler JW, Mao L, Rosenberg PB, Rockman HA, et al. (2020). The beta-arrestin-biased beta-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility. Proceedings of the National Academy of Sciences of the United States of America .
Kirchhoff C, Osterhoff C, Samalecos A (2008). HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia.Reproduction 136 (2): 235-245.
Kishore A, Hall RA (2017). Disease-associated extracellular loop mutations in the adhesion G protein-coupled receptor G1 (ADGRG1; GPR56) differentially regulate downstream signaling. The Journal of biological chemistry292 (23): 9711-9720.
Kishore A, Purcell RH, Nassiri-Toosi Z, Hall RA (2016). Stalk-dependent and Stalk-independent Signaling by the Adhesion G Protein-coupled Receptors GPR56 (ADGRG1) and BAI1 (ADGRB1). J Biol Chem 291 (7): 3385-3394.
Kleppisch T, Nelson MT (1995). Adenosine activates ATP-sensitive potassium channels in arterial myocytes via A2 receptors and cAMP-dependent protein kinase.Proceedings of the National Academy of Sciences of the United States of America 92 (26): 12441-12445.
Komolov KE, Du Y, Duc NM, Betz RM, Rodrigues J, Leib RD, et al. (2017). Structural and Functional Analysis of a beta2-Adrenergic Receptor Complex with GRK5. Cell169 (3): 407-421 e416.
Krausz C, Riera-Escamilla A (2018). Genetics of male infertility. Nature reviews. Urology15 (6): 369-384.
Krege JH, John SW, Langenbach LL, Hodgin JB, Hagaman JR, Bachman ES, et al. (1995). Male-female differences in fertility and blood pressure in ACE-deficient mice.Nature 375 (6527): 146-148.
Krejcirova R, Manasova M, Sommerova V, Langhamerova E, Rajmon R, Manaskova-Postlerova P (2018). G protein-coupled estrogen receptor (GPER) in adult boar testes, epididymis and spermatozoa during epididymal maturation.International journal of biological macromolecules 116:113-119.
Kumari P, Srivastava A, Banerjee R, Ghosh E, Gupta P, Ranjan R, et al. (2016). Functional competence of a partially engaged GPCR-beta-arrestin complex. Nature communications 7: 13416.
Lammermann T, Kastenmuller W (2019). Concepts of GPCR-controlled navigation in the immune system.Immunological reviews 289 (1): 205-231.
Langford KG, Zhou Y, Russell LD, Wilcox JN, Bernstein KE (1993). Regulated expression of testis angiotensin-converting enzyme during spermatogenesis in mice.Biology of reproduction 48 (6): 1210-1218.
Lefkowitz RJ, Shenoy SK (2005). Transduction of receptor signals by beta-arrestins. Science308 (5721): 512-517.
Leung PS, Sernia C (2003). The renin-angiotensin system and male reproduction: new functions for old hormones. Journal of molecular endocrinology30 (3): 263-270.
Li T, Yu B, Liu Z, Li J, Ma M, Wang Y, et al. (2018). Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury.Nature communications 9 (1): 11.
Li XY, Lu Y, Sun HY, Wang JQ, Yang J, Zhang HJ, et al. (2010). G protein-coupled receptor 48 upregulates estrogen receptor alpha expression via cAMP/PKA signaling in the male reproductive tract. Development137 (1): 151-157.
Liebscher I, Schoneberg T, Promel S (2013). Progress in demystification of adhesion G protein-coupled receptors. Biological chemistry 394 (8):937-950.
Liu CH, Gong Z, Liang ZL, Liu ZX, Yang F, Sun YJ, et al. (2017). Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.Nature communications 8: 14335.
Lu P, Wang F, Song X, Liu Y, Zhang K, Cao N (2016). Relative abundance of G protein-coupled receptor 30 and localization in testis and epididymis of sheep at different developmental stages. Animal reproduction science 175:10-17.
Lucas TF, Royer C, Siu ER, Lazari MF, Porto CS (2010). Expression and signaling of G protein-coupled estrogen receptor 1 (GPER) in rat sertoli cells. Biology of reproduction83 (2): 307-317.
Luo J, Yang Z, Ma Y, Yue Z, Lin H, Qu G, et al. (2016). LGR4 is a receptor for RANKL and negatively regulates osteoclast differentiation and bone resorption. Nature medicine 22 (5): 539-546.
Luttrell LM, Ferguson SS, Daaka Y, Miller WE, Maudsley S, Della Rocca GJ, et al. (1999). Beta-arrestin-dependent formation of beta2 adrenergic receptor-Src protein kinase complexes. Science 283 (5402):655-661.
Lymperopoulos A (2018). Arrestins in the Cardiovascular System: An Update. Progress in molecular biology and translational science 159: 27-57.
Lymperopoulos A, Wertz SL, Pollard CM, Desimine VL, Maning J, McCrink KA (2019). Not all arrestins are created equal: Therapeutic implications of the functional diversity of the beta-arrestins in the heart. World journal of cardiology11 (2): 47-56.
Malivindi R, Aquila S, Rago V (2018). Immunolocalization of G Protein-Coupled Estrogen Receptor in the Pig Epididymis. Anat Rec (Hoboken) .
Manglik A, Wingler LM, Rockman HA, Lefkowitz RJ (2020). beta-Arrestin-Biased Angiotensin II Receptor Agonists for COVID-19. Circulation .
Martinez-Traverso GB, Pearl CA (2015). Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis. Reproductive biology and endocrinology : RB&E13: 48.
McGeoch RJ, Oldroyd KG (2008). Pharmacological options for inducing maximal hyperaemia during studies of coronary physiology. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 71 (2): 198-204.
Menad R, Fernini M, Smai S, Bonnet X, Gernigon-Spychalowicz T, Moudilou E, et al. (2017). GPER1 in sand rat epididymis: Effects of seasonal variations, castration and efferent ducts ligation. Animal reproduction science 183: 9-20.
Mendive F, Laurent P, Van Schoore G, Skarnes W, Pochet R, Vassart G (2006). Defective postnatal development of the male reproductive tract in LGR4 knockout mice.Developmental biology 290 (2): 421-434.
Miller WE, Maudsley S, Ahn S, Khan KD, Luttrell LM, Lefkowitz RJ (2000). beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis.The Journal of biological chemistry 275 (15):11312-11319.
Minelli A, Miscetti P, Allegrucci C, Mezzasoma I (1995). Evidence of A1 adenosine receptor on epidydimal bovine spermatozoa. Archives of biochemistry and biophysics322 (1): 272-276.
Mundell S, Kelly E (2011). Adenosine receptor desensitization and trafficking. Biochimica et biophysica acta 1808 (5): 1319-1328.
O’Dea A, Sondergard C, Sweeney P, Arnatt CK (2018). A Series of Indole-Thiazole Derivatives Act as GPER Agonists and Inhibit Breast Cancer Cell Growth. ACS medicinal chemistry letters 9 (9): 901-906.
Obermann H, Samalecos A, Osterhoff C, Schroder B, Heller R, Kirchhoff C (2003). HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia. Molecular reproduction and development64 (1): 13-26.
Paavola KJ, Hall RA (2012). Adhesion G protein-coupled receptors: signaling, pharmacology, and mechanisms of activation. Molecular pharmacology 82 (5):777-783.
Paavola KJ, Stephenson JR, Ritter SL, Alter SP, Hall RA (2011). The N terminus of the adhesion G protein-coupled receptor GPR56 controls receptor signaling activity.The Journal of biological chemistry 286 (33):28914-28921.
Patat O, Pagin A, Siegfried A, Mitchell V, Chassaing N, Faguer S, et al. (2016). Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens.American journal of human genetics 99 (2):437-442.
Pereira MF, Fernandes SA, Nascimento AR, Siu ER, Hess RA, Oliveira CA, et al. (2014). Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium. Andrology2 (4): 559-571.
Peterson YK, Luttrell LM (2017). The Diverse Roles of Arrestin Scaffolds in G Protein-Coupled Receptor Signaling. Pharmacological reviews 69 (3):256-297.
Prossnitz ER, Arterburn JB, Sklar LA (2007). GPR30: A G protein-coupled receptor for estrogen.Molecular and cellular endocrinology 265-266: 138-142.
Purcell RH, Hall RA (2018). Adhesion G Protein-Coupled Receptors as Drug Targets. Annual review of pharmacology and toxicology 58: 429-449.
Qian Y, Liu S, Guan Y, Pan H, Guan X, Qiu Z, et al. (2013). Lgr4-mediated Wnt/beta-catenin signaling in peritubular myoid cells is essential for spermatogenesis.Development 140 (8): 1751-1761.
Rago V, Romeo F, Giordano F, Ferraro A, Carpino A (2016). Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland. Andrology4 (1): 121-127.
Rago V, Romeo F, Giordano F, Malivindi R, Pezzi V, Casaburi I, et al. (2018). Expression of oestrogen receptors (GPER, ESR1, ESR2) in human ductuli efferentes and proximal epididymis. Andrology 6 (1): 192-198.
Reiter E, Lefkowitz RJ (2006). GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling. Trends in endocrinology and metabolism: TEM17 (4): 159-165.
Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER (2005). A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science307 (5715): 1625-1630.
Ritter SL, Hall RA (2009). Fine-tuning of GPCR activity by receptor-interacting proteins.Nature reviews. Molecular cell biology 10 (12):819-830.
Saez F, Legare C, Laflamme J, Sullivan R (2004). Vasectomy-dependent dysregulation of a local renin-angiotensin system in the epididymis of the cynomolgus monkey (Macaca fascicularis). Journal of andrology25 (5): 784-796.
Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, et al. (2017). A comprehensive map of molecular drug targets. Nature reviews. Drug discovery16 (1): 19-34.
Shukla AK, Westfield GH, Xiao K, Reis RI, Huang LY, Tripathi-Shukla P, et al. (2014). Visualization of arrestin recruitment by a G-protein-coupled receptor.Nature 512 (7513): 218-222.
Shum WW, Da Silva N, Brown D, Breton S (2009). Regulation of luminal acidification in the male reproductive tract via cell-cell crosstalk. The Journal of experimental biology 212 (Pt 11): 1753-1761.
Shum WW, Da Silva N, McKee M, Smith PJ, Brown D, Breton S (2008). Transepithelial projections from basal cells are luminal sensors in pseudostratified epithelia. Cell135 (6): 1108-1117.
Sibony M, Segretain D, Gasc JM (1994). Angiotensin-converting enzyme in murine testis: step-specific expression of the germinal isoform during spermiogenesis. Biology of reproduction 50 (5): 1015-1026.
Smith JS, Lefkowitz RJ, Rajagopal S (2018). Biased signalling: from simple switches to allosteric microprocessors. Nature reviews. Drug discovery17 (4): 243-260.
Sounier R, Mas C, Steyaert J, Laeremans T, Manglik A, Huang W, et al. (2015). Propagation of conformational changes during mu-opioid receptor activation.Nature 524 (7565): 375-378.
Speth RC, Daubert DL, Grove KL (1999). Angiotensin II: a reproductive hormone too? Regulatory peptides 79 (1): 25-40.
Srivastava A, Gupta B, Gupta C, Shukla AK (2015). Emerging Functional Divergence of beta-Arrestin Isoforms in GPCR Function. Trends in endocrinology and metabolism: TEM 26 (11): 628-642.
Staus DP, Hu H, Robertson MJ, Kleinhenz ALW, Wingler LM, Capel WD, et al. (2020). Structure of the M2 muscarinic receptor-beta-arrestin complex in a lipid nanodisc.Nature 579 (7798): 297-302.
Sun JP, Li R, Ren HZ, Xu AT, Yu X, Xu ZG (2013). The very large G protein coupled receptor (Vlgr1) in hair cells. Journal of molecular neuroscience : MN50 (1): 204-214.
Szentmiklosi AJ, Galajda Z, Cseppento A, Gesztelyi R, Susan Z, Hegyi B, et al. (2015). The Janus face of adenosine: antiarrhythmic and proarrhythmic actions.Current pharmaceutical design 21 (8): 965-976.
Thomas P, Pang Y, Filardo EJ, Dong J (2005). Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology146 (2): 624-632.
Tobin AB, Butcher AJ, Kong KC (2008). Location, location, location…site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling.Trends in pharmacological sciences 29 (8):413-420.
van Galen PJ, Stiles GL, Michaels G, Jacobson KA (1992). Adenosine A1 and A2 receptors: structure–function relationships. Medicinal research reviews12 (5): 423-471.
Van Schoore G, Mendive F, Pochet R, Vassart G (2005). Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse. Histochemistry and cell biology124 (1): 35-50.
Venkatakrishnan AJ, Deupi X, Lebon G, Heydenreich FM, Flock T, Miljus T, et al. (2016). Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region. Nature 536 (7617):484-487.
Wang W, Qiao Y, Li Z (2018). New Insights into Modes of GPCR Activation. Trends in pharmacological sciences 39 (4): 367-386.
Wang XJ, Zhang DL, Xu ZG, Ma ML, Wang WB, Li LL, et al. (2014). Understanding cadherin EGF LAG seven-pass G-type receptors. Journal of neurochemistry131 (6): 699-711.
Wingler LM, Skiba MA, McMahon C, Staus DP, Kleinhenz ALW, Suomivuori CM, et al. (2020). Angiotensin and biased analogs induce structurally distinct active conformations within a GPCR. Science 367 (6480):888-892.
Winters BR, Walsh TJ (2014). The epidemiology of male infertility. The Urologic clinics of North America 41 (1): 195-204.
Wong PY, Uchendu CN (1990). The role of angiotensin-converting enzyme in the rat epididymis. The Journal of endocrinology 125 (3): 457-465.
Xiao K, McClatchy DB, Shukla AK, Zhao Y, Chen M, Shenoy SK, et al. (2007). Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 104 (29): 12011-12016.
Yang B, Wang J, Zhang W, Pan H, Li T, Liu B, et al. (2017a). Pathogenic role of ADGRG2 in CBAVD patients replicated in Chinese population. Andrology5 (5): 954-957.
Yang F, Xiao P, Qu CX, Liu Q, Wang LY, Liu ZX, et al. (2018). Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through arrestin. Nature chemical biology 14 (9): 876-886.
Yang F, Yu X, Liu C, Qu CX, Gong Z, Liu HD, et al. (2015). Phospho-selective mechanisms of arrestin conformations and functions revealed by unnatural amino acid incorporation and (19)F-NMR. Nature communications 6:8202.
Yang Z, Yang F, Zhang D, Liu Z, Lin A, Liu C, et al. (2017b). Phosphorylation of G Protein-Coupled Receptors: From the Barcode Hypothesis to the Flute Model.Molecular pharmacology 92 (3): 201-210.
Yi J, Xiong W, Gong X, Bellister S, Ellis LM, Liu Q (2013). Analysis of LGR4 receptor distribution in human and mouse tissues. PloS one 8 (10): e78144.
Yuan P, Liang ZK, Liang H, Zheng LY, Li D, Li J, et al. (2019). Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles. Andrology7 (3): 329-340.
Zhang DL, Sun YJ, Ma ML, Wang YJ, Lin H, Li RR, et al. (2018). Gq activity- and beta-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility. eLife 7 .
Zhao W, Leung PY, Chew SB, Chan HC, Wong PY (1996). Localization and distribution of angiotensin II in the rat epididymis. The Journal of endocrinology149 (2): 217-222.
Zhou W, De Iuliis GN, Dun MD, Nixon B (2018). Characteristics of the Epididymal Luminal Environment Responsible for Sperm Maturation and Storage. Frontiers in endocrinology 9: 59.