Potential Role of Plasmalogens in the Modulation of Biomembrane Morphology

Plasmalogens are a subclass of cell membrane glycerophospholipids that typically include vinyl- ether bond at the sn-1 position and polyunsaturated fatty acid at the sn-2 position. They are highly abundant in the neuronal, immune, and cardiovascular cell membranes. Despite the abundance of plasmalogens in a plethora of cells, tissues, and organs, the role of plasmalogens remains unclear. Plasmalogens are required for the proper function of integral membrane proteins, lipid rafts, cell signaling, and differentiation. More importantly, plasmalogens play a crucial role in the cell as an endogenous antioxidant that protects the cell membrane components such as phospholipids, unsaturated fatty acids, and lipoproteins from oxidative stress. The incorporation of vinyl-ether linked with alkyl chains in phospholipids alter the physicochemical properties (e.g., the hydrophilicity of the headgroup), packing density, and conformational order of the phospholipids within the biomembranes. Thus, plasmalogens play a significant role in determining the physical and chemical properties of the biomembrane such as its fluidity, thickness, and lateral pressure of the biomembrane. Insights on the important structural and functional properties of plasmalogens may help us to understand the molecular mechanism of membrane transformation, vesicle formation, and vesicular fusion, especially at the synaptic vesicles where plasmalogens are rich and essential for neuronal function. Although many aspects of plasmalogen phospholipid involvement in membrane transformation identified through in vitro experiments and membrane mimic systems, remain to be confirmed in vivo, the compiled data show many intriguing properties of vinyl-ether bonded lipids that may play a significant role in the structural and morphological changes of the biomembranes. In this review, we present the current limited knowledge of the emerging potential role of plasmalogens as a modulator of the biomembrane morphology.

Sex steroids influence the plasma membrane transformation in the uterus of the fat-tailed dunnart (Sminthopsis crassicaudata, Marsupialia)

The uterine epithelium undergoes remodelling to become receptive to blastocyst implantation during pregnancy in a process known as the plasma membrane transformation. There are commonalities in ultrastructural changes to the epithelium, which, in eutherian, pregnancies are controlled by maternal hormones, progesterone and oestrogens. The aim of this study was to determine the effects that sex steroids have on the uterine epithelium in the fat-tailed dunnart Sminthopsis crassicaudata, the first such study in a marsupial. Females were exposed to exogenous hormones while they were reproductively quiescent, thus not producing physiological concentrations of ovarian hormones. We found that changes to the protein E-cadherin, which forms part of the adherens junction, are controlled by progesterone and that changes to the desmoglein-2 protein, which forms part of desmosomes, are controlled by 17β-oestradiol. Exposure to a combination of progesterone and 17β-oestradiol causes changes to the microvilli on the apical surface and to the ultrastructure of the uterine epithelium. There is a decrease in lateral adhesion when the uterus is exposed to progesterone and 17β-oestradiol that mimics the hormone environment of uterine receptivity. We conclude that uterine receptivity and the plasma membrane transformation in marsupial and eutherian pregnancies are under the same endocrine control and may be an ancestral feature of therian mammals.

446. Ezrin and EBP50 relocate apically in rat uterine epithelial cells during contact with opposing cells, except cells contacting the blastocyst

Uterine epithelial cells are important in constantly maintaining a tissue protective barrier, and only under the specific hormonal conditioning of pregnancy which involves a remodelling of the cell ultrastructure termed the 'plasma membrane transformation'. This allows for the successful invasion of the blastocyst. Indirect immunofluorescence microscopy in rat uterine epithelial cells during pregnancy shows that ezrin and EBP50 are relocated to the apical membrane upon lumen closure at the time of implantation, and on average results in 90% colocalisation. Ezrin and EBP50 function as a linked protein complex at the time of implantation seen through immunoprecipitation results from day 6 of pregnancy. The ezrin-EBP50 complex is also associated with the membrane, shown using cell fractionation and western blotting analysis in which ezrin increased dramatically in the membrane concentrated fraction, and correspondingly decreased in the cytosolic fraction leading up to implantation. At the apical membrane these proteins are likely associating with intra-membranous signalling molecules which allow communication between contacting cells. The same protein complex is also relocated to the apical membrane when cells contact an inanimate filament inserted into the uterus of a non-pregnant rat. The only unique contacting circumstance in which these proteins are not seen at the apical membrane is within the implantation chamber itself, more specifically the cells in direct contact with the implanting blastocyst. These results highlight the unique situation that is implantation, which involves specific blastocyst signalling and influence upon the uterine epithelial cells lining the implantation chamber. It may be that the ezrin-EBP50 protein complex is critical at the earlier stage of apposition, and through blastocyst influence, are subsequently lost from the apical membrane to allow for successful invasion.