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Details on Person Aldosterone can also elicit very rapid actions within minute...
| Class:Id | Summation:9037082 |
|---|---|
| _displayName | Aldosterone can also elicit very rapid actions within minute... |
| _timestamp | 2018-03-30 19:56:54 |
| created | [InstanceEdit:9037092] Shamovsky, Veronica, 2018-02-16 |
| modified | [InstanceEdit:9604038] Shamovsky, Veronica, 2018-03-30 |
| text | Aldosterone can also elicit very rapid actions within minutes that do not require transcription or translation and that occur in kidney and colon but also in nonepithelial tissues like heart, vasculature and adipose tissue. Most of these effects can be mediated by classical MR and its crosstalk with different signaling cascades. Near the plasma membrane, the MR seems to be associated with caveolin and striatin bind to MR attached to the plasma membrane by scaffolding proteins like Cav1 and striatin. The caveolin-binding domain of striatin can directly bind to caveolin-1 (CAV1), a scaffolding protein within the caveolar membrane that can associate with an interaction of the MR with the EGF receptor (a membrane spanning receptor) has been shown (Grossmann et al., 2010). Importantly, disruption of caveolae-like lipid rafts inhibited this interaction, which strongly suggests MR-membrane localization in this system. a direct association between the MR and caveolin-1 (but not caveolin-2) was shown with co-immunoprecipitation in heart homogenates from both rat and mouse as well as in cultured human endothelial cells (Pojoga et al., 2010b). As expected, this association was lost in cav1−/− mice. Secondly, these mice showed heightened vascular responses to treatment with the MR antagonist eplerenone (as compared to wildtype mice) (Pojoga et al., 2010a) and a reduced sensitivity to aldosterone treatment on myocardial damage (Pojoga et al., 2010b). Thus, not only is the MR associated with caveolin-1 in vascular tissues, but a loss of caveolin-1 also alters the vascular responses to MR agonists and antagonists. ransfection of only the ligand binding domain of the MR was sufficient for aldosterone to rapidly activate the ERK1/2 pathway in Chinese hamster ovary cells (Grossmann et al., 2008). the colocalization between the MR and the EGF receptor. This colocalization was lost when lipid rafts (including caveolae) were disrupted (Grossmann et al., 2010). This strongly suggests that the MR is localized in caveolae, since the EGF receptor is known to be associated with caveolae. MR does not contain a perfect palmitoylation sequence which has been shown to be required for membrane localization of ER, PR and AR. The MR, by contrast, lacks the essential cysteine residue. As this cysteine provides the thiol group to which the palmitate tail is transferred, the MR cannot be palmitoylated at this sequence (GRossmann C et al. 2009). The membrane fraction of MR is not stable but dissociates slowly under conditions of prolonged activation with saturating concentrations of aldosterone and also moves into the nucleus. These data are in agreement with the observed disappearance of MR from the membrane fraction of HEK-MR cells after prolonged aldosterone exposure (Ziera T et al. 2009). |
| (summation) | [Reaction:9037093] NR3C2 binds STRN, CAV1 [Homo sapiens] |
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No pathways have been reviewed or authored by Aldosterone can also elicit very rapid actions within minute... (9037082)
