User:Bio phys 568/Membrane estrogen receptor

'// the original article just had an introduction that had like 3 sentences, one of them factually incorrect. I've reworked the intro (my version below) and updated the actual page with it; everything from "Structure-function relationship" on is my outline of additional changes I'm planning/thinking about.''' ''

Membrane estrogen receptors (mERs) are estrogen-binding receptors located in the plasma membrane. Unlike nuclear estrogen receptors, which mediate their effects via slower genomic mechanisms, mERs are cell surface receptors that rapidly alter cell signaling via modulation of intracellular signaling cascades.

Nuclear estrogen receptors such as ERα and ERβ can become mERs through palmitoylation, a post-translational modification that enhances ER association with caveolin-1, which then traffics ERs to membrane caveolae. Other putative mERs include GPER (GPR30), GPRC6A, ER-X, ERx and Gq-mER.

Structure-function relationship
In mice and humans, ERβ localization in the plasma membrane occurs after palmitoylation on cysteine 418. Dimerization of mERs appears necessary for their function in rapid cell signaling.
 * Post-translational modifications: Any post-translational modifications that the receptor undergoes, such as glycosylation or phosphorylation.
 * Oligomeric state: Whether the receptor exists as a monomer or as part of an oligomeric complex.
 * Structure-function relationships: A discussion of how the receptor's structure relates to its function.

G-protein coupled receptors
Various electrophysiological studies support E2 signaling via GPCRs. mERs are thought to activate G-protein coupled receptors to regulate L-type Ca2+ channels and activate protein kinase A (PKA), protein kinase C (PKC), and mitogen activated protein kinase (MAPK) signalling cascades. ).

Gq-coupled mERs (Gq-mERs) activation has been demonstrated to rapidly increase membrane excitability various neuronal cell types by desensitizing GABAB receptor coupling to G protein-coupled inwardly rectifying K+ channels (GIRKs).

RTKs
- MAP/ERK

-PI3K/AKT

mGluRs
Localization of mERs in caveolae allows them to be held in close proximity to specific receptors such as mGluRs. Various studies have demonstrated mER's ability to activate mGluR signaling, even in the absence of glutamate. ER/mGluR signaling is thought to be highly relevant for female motivational behavior. Interestingly, modification of caveolin expression appears to alter the nature of ER-mGluR interactions.

(more)

Other stuff to mention?
Further information: Estrogen receptor

- Subunits

- homo and heterodimers

- Ligands

- Signal transduction

- Function/malfunction

- neural (mesocorticolimbic DA pathway?)

- other... bodily things

Ligands
- estrogen

Brain
- ventral vs dorsal striatum

Other tissues i guess
blah blah...

Clinical significance(?)
Membrane estrogen receptors have been implicated in reproductive, cardiovascular, neural, and immune function, including cancer, neurodegenerative disease, and cardiovascular disorders(CITE).

Cancer
GPER1 pathways modify local inflammation and strengthen cellular immune responses in breast cancer and melanoma, making it a strong prognostic marker.

Neurodegenerative disease
mERs have a demonstrated neuroprotective effect on A classic example of estrogen has been demonstrated to have neurotrophic and neuroprotective effects.

Cardiovascular disorders
mERβ has been demonstrated to mitigate cardiac cell pathology caused by angiotensin II. Activation of mER but not nuclear ER signaling in vascular epithelial cells promotes protection against vascular injury in mice. Striatin, a scaffolding protein that links mERs to membrane caveolae, is necessary for this effect.

Addiction
Propensity to addiction appears to be mediated by sex hormones such as estrogen. In neural reward circuity, nuclear ERs are not commonly expressed, and mERs have been demonstrated to act on mGluR5 to facilitate psychostimulant-induced behavioral and neurochemical effects.