Angiotensin II AT2 receptor oligomers mediate G-protein dysfunction in an animal model of Alzheimer disease.

Progressive neurodegeneration and decline of cognitive functions are major hallmarks of Alzheimer disease (AD). Neurodegeneration in AD correlates with dysfunction of diverse signal transduction mechanisms, such as the G-protein-stimulated phosphoinositide hydrolysis mediated by Galphaq/11. We report here that impaired Galphaq/11-stimulated signaling in brains of AD patients and mice correlated with the appearance of cross-linked oligomeric angiotensin II AT2 receptors sequestering Galphaq/11.

Dominant negative AT2 receptor oligomers induce G-protein arrest and symptoms of neurodegeneration.

Neurodegeneration in Alzheimer's disease (AD) correlates with dysfunction of signaling mediated by Galphaq/11. Nondissociable angiotensin II AT2 receptor oligomers are linked to the impaired Galphaq/11-stimulated signaling of AD patients and transgenic mice with AD-like symptoms. To further analyze the role of AT2 receptor oligomers, we induced the formation of AT2 oligomers in an in vitro cell system.

Mesangial AT1/B2 receptor heterodimers contribute to angiotensin II hyperresponsiveness in experimental hypertension.

Angiotensin II plays a central role in the pathogenesis of hypertension and of related cardiovascular disorders by binding to and activating angiotensin II receptors (AT1 receptors). Sensitization to the vasopressor response of angiotensin II is a key feature in many cardiovascular disorders. However, underlying mechanisms responsible for angiotensin II hypersensitivity are barely understood.

Factor XIIIA transglutaminase crosslinks AT1 receptor dimers of monocytes at the onset of atherosclerosis.

Many G protein-coupled receptors form dimers in cells. However, underlying mechanisms are barely understood. We report here that intracellular factor XIIIA transglutaminase crosslinks agonist-induced AT1 receptor homodimers via glutamine315 in the carboxyl-terminal tail of the AT1 receptor.

AT1 receptor heterodimers and angiotensin II responsiveness in preeclampsia.

Preeclampsia is a pregnancy-specific hypertensive disorder with unknown etiology, which affects 5% to 10% of all pregnancies. Increased sensitivity to the vasoconstrictor angiotensin II is a common feature of preeclampsia, although underlying mechanisms are barely understood. Recent data reveal a potential mechanism for the increased angiotensin II responsiveness in preeclampsia: increased levels of heterodimers between the vasopressor receptor AT1 and the vasodepressor receptor B2.