Membrane phospholipid synthesis and endoplasmic reticulum function

Abstract

This review presents an overview of mammalian phospholipid synthesis and the cellular locations of the biochemical activities that produce membrane lipid molecular species. The generalized endoplasmic reticulum compartment is a central site for membrane lipid biogenesis, and examples of the emerging relationships between alterations in lipid composition, regulation of membrane lipid biogenesis, and cellular secretory function are discussed.-Fagone, P., and S. Jackowski. BIOLOGICAL MEMBRANESBiological membranes are composed of lipids and proteins that together form hydrophobic barriers that limit the distribution of aqueous macromolecules and metabolites. Cells use membranes for a number of different purposes, including segregation and protection from the environment, compartmentalization of functions, energy production, storage, protein synthesis and secretion, phagocytosis, movement, and cell-cell interaction. Eukaryotic cells contain ordered infrastructures, called organelles, to organize and carry out complex processes and to enable distinct reactions that require a hydrophobic environment. The level and complexity of compartmentalization varies among organisms and among mammalian cells. Some cells also change in size and organelle complexity after biological stimulation. An example of induced membrane biogenesis occurs in naïve B-lymphocytes that are converted to plasma cells (1), and an example of membrane redistribution occurs in macrophages in which the Golgi apparatus is reoriented during transient cytokine synthesis and secretion (2). The versatility of biological membranes is dependent on their structures and biophysical properties, which are dictated by the types of lipids and proteins that compose the membranes. The functions of membranes require a fluid plasticity that is accomplished through alteration in lipid composition. Lipid composition is diverse, not only among different organisms, but also among different compartments within the same cells and between the two leaflets of the same membrane. Lipid composition is determined through regulation of de novo synthesis at designated cellular sites, selective distribution or trafficking to new sites, and by localized remodeling reactions. Understanding the relationships between the dynamic changes in membrane lipid composition and specific cellular events is our current challenge. This review is focused on membrane phospholipid biogenesis in mammalian cells with a particular emphasis on the role played by the endoplasmic reticulum (ER). The ER, together with the Golgi apparatus, is a major site of de novo bulk membrane lipid synthesis, and recent experiments demonstrate a link between phospholipid synthesis and secretion from this compartment. THE ARCHITECTURE OF THE ERThe ER and Golgi apparatus together constitute the endomembrane compartment in the cytoplasm of eukaryotic cells. The endomembrane compartment is a major site of lipid synthesis, and the ER is where not only lipids are synthesized, but membrane-bound proteins and secretory pr...

Behaviour of NBD-head group labelled phosphatidylethanolamines in POPC bilayers: a molecular dynamics study

“…In numerical terms, this apparently puzzling result stems from the fact that -S CD of the second-neighbouring (0.4 nm o R o 0.8 nm) and bulk POPC chains (R 4 0.8 nm) is increased compared to pure POPC. Because there are considerably more POPC chains in these more distant R value ranges, overall averages tend to be slightly (consistently for all probes except NBD-diC 4 PE, but within the statistical uncertainty for n o 14) higher for probe-loaded bilayers than for pure lipid. In physical terms, this result excludes the possibility of the inserted anionic probes being the main responsible species for the overall membrane ordering in most systems.…”

“…17 For a related homologous series (fatty amines NBD-C n ), we obtained a linear variation of partition free energy with chain length, with slope DDG = À(2.4 AE 0.2) kJ mol À1 . 55,56 From these values, we may extrapolate log K p = 1.6 for NBD-diC 4 PE, corresponding to 495% of bilayer-inserted molecules of this solute (and 499% of all other amphiphiles of the series) under conditions replicating the setting of our simulations. Still, it is entirely possible that, for much longer simulations, the occasional passage of the shorter amphiphiles to the water phase could be observed.…”

“…[1][2][3] Additionally, the involvement of biomembranes in several cellular processes, including energy production, protein synthesis and secretion, signal transduction and cell-cell interactions has been evidenced more recently. 3,4 Among the arsenal of techniques used to study membrane structure and function, fluorescence-based methodologies are most prominent. This role is warranted by the inherent sensitivity of fluorescence (down to single molecule level), coupled with the versatility resulting from the multiplicity of different spectroscopic and imaging fluorescence approaches.…”

Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown

“…The outer membrane and lumen of the nuclear envelope are directly contiguous with other ER structural elements, whereas passage of proteins to the inner nuclear membrane (INM) is gated by the nuclear pores (Hetzer 2010;English and Voeltz 2013). The chromatin-facing INM is associated with the nuclear lamina, a dense filament meshwork that provides structural support (Hetzer 2010;Gerace and Huber 2012).The ER also serves as a platform for de novo phospholipid synthesis (Fagone and Jackowski 2009;Lagace and Ridgway 2013). A central player is the conserved phosphatase lipin, which converts phosphatidic acid (PA) to diacylglycerol (DAG) Siniossoglou 2013).…”

“…The ER also serves as a platform for de novo phospholipid synthesis (Fagone and Jackowski 2009;Lagace and Ridgway 2013). A central player is the conserved phosphatase lipin, which converts phosphatidic acid (PA) to diacylglycerol (DAG) Siniossoglou 2013).…”