Membrane lipid rafts and estrogenic signalling: a functional role in the modulation of cell homeostasis

Abstract

It has become widely accepted that along with their ability to directly regulate gene expression, estrogens also influence cell signalling and cell function via rapid membrane-initiated events. Many of these signalling processes are dependent on estrogen receptors (ER) localized to the plasma membrane. However, the mechanisms by which ER are able to trigger cell signalling when targeted to the membrane surface have to be determined yet. Lipid rafts seem to be essential for the plasma membrane localization of ER and play a critical role in their membrane-initiated effects. In this review, we briefly recapitulate the localization and function of ER in different cell types and mostly discuss the possible role of lipid rafts in this context. Further studies in this field may disclose new promising therapeutic avenues by the disruption of lipid rafts in those diseases in which membrane ER activation has been demonstrated to play a pathogenetic role.

BASP1 interacts with oestrogen receptor α and modifies the tamoxifen response

“…33, 34 It is therefore of interest that ER α associates with lipid rafts where it is suggested to regulate cellular signalling. 35 It will be interesting to determine if BASP1 also has a role in this ER α function and if this is connected with the nuclear events that we report here.…”

Self‐assembly of lipid rafts revealed by fluorescence correlation spectroscopy in living breast cancer cells

“…The centre of order peak in the double Gauss distribution was significantly increased from 0.346 ± 0.006 to 0.378 ± 0.008 ( Figure 4G), indicating that β-estradiol could effectively change the membrane phase from Ld phase to Lo phase. The results indicated that the plasma membrane could preferentially recruit proteins and lipids to generate the rafts domains and then further affect their lipids diffusion [3,6,17]. The results indicated that the plasma membrane could preferentially recruit proteins and lipids to generate the rafts domains and then further affect their lipids diffusion [3,6,17].…”

“…The β-estradiol could enhance the association of oestrogen receptors with the membrane rafts and induce rapid phosphorylation to trigger the nuclear receptor coactivator [5,6]. Herein, the membrane phase and lipid The effect of β-estradiol on membrane phase were visualised through GP imaging ( Figure 4A,B).…”

“…The lipid rafts are dynamic assemblies of proteins and lipids (in terms of both lateral mobility and association-dissociation) and act as functional signal transduction platforms for the regulation of cellular processes. Hence, obtaining the dynamic properties of lipid rafts in specific physiological processes has an irreplaceable role to understand the structure and function of lipid rafts [4][5][6][7][8][9]. Recently, several biochemical and biophysical properties of lipid rafts have provided support for the presence of these domains and showed their key roles for membrane heterogeneity in various cellular functions.…”

The role of sphingolipids and lipid rafts in determining cell fate

“…Thus, they can act as catalytic domains where molecular interactions can be facilitated and contribute to the triggering of signaling cascades involved not only in apoptosis, but also in proliferation, differentiation, stress responses, necrosis, inflammation, autophagy, and senescence. In particular, the work by Maselli et al [9] describe how the so-called non-nuclear receptors for estrogen are embedded in lipid rafts and can serve as a cell membraneinitiated events providing a prompt response and activating survival intracellular pathways such as autophagy. This Issue is thus devoted to the analysis of different aspects underlying the implication of sphingolipids and lipid microdomains in cell pathophysiology: from their synthesis and assembly to their metabolic pathways and to their impact either on cell death by apoptosis or in autophagic process.…”