Penile erection is a complicated event involving the regulation of corpus cavernosal smooth muscle tone. Recently, the small monomeric G-protein RhoA and its downstream effector Rho-kinase have been proposed to be important players for mediating vasoconstriction in the penis. RhoA/Rho-kinase increases MLC (myosin light chain) phosphorylation through inhibition of MLCP (MLC phosphatase) thereby increasing Ca2+ sensitivity. This review will outline the RhoA/Rho-kinase signalling pathway, including the upstream regulators, guanine nucleotide exchange factors, GDP dissociation inhibitors and GTPase-activating proteins. We also summarize the current knowledge about the physiological roles of RhoA/Rho-kinase in both male and female erectile tissues and its aberrations contributing to erectile dysfunction in several disease states. Understanding the RhoA/Rho-kinase signalling pathway in the regulation of erection is important for the development of therapeutic interventions for erectile dysfunction.
- corpus cavernosum
- erectile dysfunction
- smooth muscle
Abbreviations: CNF, cytotoxic necrotizing factor; DAG, diacylglycerol; DH, Dbl homology; ED, erectile dysfunction; ET-1, endothelin-1; GAP, GTPase-activating protein; GDI, GDP dissociation inhibitor; GEF, guanine nucleotide exchange factor; GPCR, G-protein-coupled receptor; GTP[S], guanosine 5-[γ-thio]triphosphate; ICP, intracavernosal pressure; IP3, inositol trisphosphate; LARG, leukaemia-associated RhoGEF; MLC, myosin light chain; MLCK, MLC kinase; MLCP, MLC phosphatase; MMAS, Massachusetts Male Aging Study; NO, nitric oxide; NOS, NO synthase; eNOS, endothelial NOS; PH, pleckstrin homology; PIP2, phosphatidylinositol 4,5-bisphosphate; PKA, cAMP-dependent protein kinase A; PKB, protein kinase B; PKC, protein kinase C; CPI-17, PKC-potentiated inhibitor protein of 17 kDa; PLC, phospholipase C; PP1, protein phosphatase 1; RGS, regulators of the G-protein signalling; SHR, spontaneously hypertensive rat; siRNA, small interference RNA; SMC, smooth muscle cell; SNP, sodium nitroprusside; WKY, Wistar–Kyoto
- The Biochemical Society