scholarly journals Contribution of Membrane Lipids to Postsynaptic Protein Organization

2021 ◽  
Vol 13 ◽  
Author(s):  
Manon Westra ◽  
Yolanda Gutierrez ◽  
Harold D. MacGillavry
Keyword(s):  
Synaptic Transmission ◽  
Protein Interactions ◽  
Membrane Lipids ◽  
Postsynaptic Membrane ◽  
Synaptic Membrane ◽  
Protein Distribution ◽  
Receptor Complexes ◽  
Postsynaptic Protein ◽  
Technical Developments ◽  
Lipid Species

The precise subsynaptic organization of proteins at the postsynaptic membrane controls synaptic transmission. In particular, postsynaptic receptor complexes are concentrated in distinct membrane nanodomains to optimize synaptic signaling. However, despite the clear functional relevance of subsynaptic receptor organization to synaptic transmission and plasticity, the mechanisms that underlie the nanoscale organization of the postsynaptic membrane remain elusive. Over the last decades, the field has predominantly focused on the role of protein-protein interactions in receptor trafficking and positioning in the synaptic membrane. In contrast, the contribution of lipids, the principal constituents of the membrane, to receptor positioning at the synapse remains poorly understood. Nevertheless, there is compelling evidence that the synaptic membrane is enriched in specific lipid species and that deregulation of lipid homeostasis in neurons severely affects synaptic functioning. In this review we focus on how lipids are organized at the synaptic membrane, with special emphasis on how current models of membrane organization could contribute to protein distribution at the synapse and synaptic transmission. Finally, we will present an outlook on how novel technical developments could be applied to study the dynamic interplay between lipids and proteins at the postsynaptic membrane.

scholarly journals Regulation of the Stability and Localization of Post-synaptic Membrane Proteins by Liquid-Liquid Phase Separation

2021 ◽  
Vol 12 ◽  
Author(s):  
Tomohisa Hosokawa ◽  
Pin-Wu Liu
Keyword(s):  
Synaptic Plasticity ◽  
Phase Separation ◽  
Liquid Phase ◽  
Synaptic Transmission ◽  
Molecular Mechanism ◽  
Postsynaptic Membrane ◽  
Liquid Phase Separation ◽  
Synaptic Membrane ◽  
The Stability ◽  
Liquid Liquid Phase Separation

Synaptic plasticity is a cellular mechanism of learning and memory. The synaptic strength can be persistently upregulated or downregulated to update the information sent to the neuronal network and form a memory engram. For its molecular mechanism, the stability of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate-type glutamate receptor (AMPAR), a glutamatergic ionotropic receptor, on the postsynaptic membrane has been studied for these two decades. Since AMPAR is not saturated on the postsynaptic membrane during a single event of neurotransmitter release, the number and nanoscale localization of AMPAR is critical for regulating the efficacy of synaptic transmission. The observation of AMPAR on the postsynaptic membrane by super-resolution microscopy revealed that AMPAR forms a nanodomain that is defined as a stable segregated cluster on the postsynaptic membrane to increase the efficacy of synaptic transmission. Postsynaptic density (PSD), an intracellular protein condensate underneath the postsynaptic membrane, regulates AMPAR dynamics via the intracellular domain of Stargazin, an auxiliary subunit of AMPAR. Recently, it was reported that PSD is organized by liquid-liquid phase separation (LLPS) to form liquid-like protein condensates. Furthermore, the calcium signal induced by the learning event triggers the persistent formation of sub-compartments of different protein groups inside protein condensates. This explains the formation of nanodomains via synaptic activation. The liquid-like properties of LLPS protein condensates are ideal for the molecular mechanism of synaptic plasticity. In this review, we summarize the recent progress in the properties and regulation of synaptic plasticity, postsynaptic receptors, PSD, and LLPS.

scholarly journals Heat stress elicits remodeling in the anther lipidome of peanut

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zolian S. Zoong Lwe ◽  
Ruth Welti ◽  
Daniel Anco ◽  
Salman Naveed ◽  
Sachin Rustgi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Heat Stress ◽  
Fatty Acid ◽  
Membrane Lipids ◽  
Fatty Acid Desaturase ◽  
Susceptible Genotype ◽  
Unsaturated Lipid ◽  
Lipid Species ◽  
Lipid Unsaturation ◽  
Fatty Acid Amount

AbstractUnderstanding the changes in peanut (Arachis hypogaea L.) anther lipidome under heat stress (HT) will aid in understanding the mechanisms of heat tolerance. We profiled the anther lipidome of seven genotypes exposed to ambient temperature (AT) or HT during flowering. Under AT and HT, the lipidome was dominated by phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TAG) species (> 50% of total lipids). Of 89 lipid analytes specified by total acyl carbons:total carbon–carbon double bonds, 36:6, 36:5, and 34:3 PC and 34:3 PE (all contain 18:3 fatty acid and decreased under HT) were the most important lipids that differentiated HT from AT. Heat stress caused decreases in unsaturation indices of membrane lipids, primarily due to decreases in highly-unsaturated lipid species that contained 18:3 fatty acids. In parallel, the expression of Fatty Acid Desaturase 3-2 (FAD3-2; converts 18:2 fatty acids to 18:3) decreased under HT for the heat-tolerant genotype SPT 06-07 but not for the susceptible genotype Bailey. Our results suggested that decreasing lipid unsaturation levels by lowering 18:3 fatty-acid amount through reducing FAD3 expression is likely an acclimation mechanism to heat stress in peanut. Thus, genotypes that are more efficient in doing so will be relatively more tolerant to HT.

scholarly journals Lipid Remodeling Confers Osmotic Stress Tolerance to Embryogenic Cells during Cryopreservation

2021 ◽  
Vol 22 (4) ◽  
pp. 2174
Author(s):  
Liang Lin ◽  
Junchao Ma ◽  
Qin Ai ◽  
Hugh W. Pritchard ◽  
Weiqi Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Technology Development ◽  
Membrane Lipids ◽  
Species Conservation ◽  
Membrane Lipid ◽  
Cell Integrity ◽  
Embryogenic Cells ◽  
Osmotic Stress Tolerance ◽  
Lipid Species ◽  
Magnolia Officinalis

Plant species conservation through cryopreservation using plant vitrification solutions (PVS) is based in empiricism and the mechanisms that confer cell integrity are not well understood. Using ESI-MS/MS analysis and quantification, we generated 12 comparative lipidomics datasets for membranes of embryogenic cells (ECs) of Magnolia officinalis during cryogenic treatments. Each step of the complex PVS-based cryoprotocol had a profoundly different impact on membrane lipid composition. Loading treatment (osmoprotection) remodeled the cell membrane by lipid turnover, between increased phosphatidic acid (PA) and phosphatidylglycerol (PG) and decreased phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The PA increase likely serves as an intermediate for adjustments in lipid metabolism to desiccation stress. Following PVS treatment, lipid levels increased, including PC and PE, and this effectively counteracted the potential for massive loss of lipid species when cryopreservation was implemented in the absence of cryoprotection. The present detailed cryobiotechnology findings suggest that the remodeling of membrane lipids and attenuation of lipid degradation are critical for the successful use of PVS. As lipid metabolism and composition varies with species, these new insights provide a framework for technology development for the preservation of other species at increasing risk of extinction.

Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog

1971 ◽  
Vol 177 (1049) ◽  
pp. 509-539 ◽  
Keyword(s):  
Synaptic Transmission ◽  
Ganglion Cells ◽  
Postsynaptic Membrane ◽  
Equilibrium Potential ◽  
Neuronal Membrane ◽  
Excitatory Postsynaptic Potential ◽  
Parasympathetic Nerve ◽  
Iontophoretic Application ◽  
Synaptic Boutons ◽  
Synaptic Transmitter

Synaptic transmission has been analysed in parasympathetic nerve cells that lie in the transparent interatrial septum of the heart of the frog. Using Nomarski interference optics, one can see much cellular detail, including synaptic boutons in living preparations. 1. On each ganglion cell, the 10 to 20 synaptic boutons are usually derived from a single vagal nerve fibre. These fibres branch extensively to innervate a number of septal ganglion cells. 2. The chemical transmitter, acetylcholine (ACh), liberated by a presynaptic impulse survives for up to 40 ms, setting up an excitatory postsynaptic potential (e.p.s.p.) which triggers one and sometimes two action potentials in the postsynaptic cell. The e.p.s.p. is made up of quantal components, as at the neuromuscular junction. 3. Nerve-evoked e.p.s.p.s can be well matched in amplitude and time course by iontophoretic application of ACh to selected areas of the neuronal membrane. In particular, the miniature e.p.s.p., which is due to the focal release of a small quantity of transmitter, was accurately mimicked by iontophoretic application of ACh. By grading the amount of ACh released from an electrode one could also duplicate the wide variety of nerve-evoked postsynaptic discharges of ganglion cells. 4. The permeability changes initiated in the postsynaptic membrane by applied ACh and the synaptic transmitter appear identical, since the ionic fluxes for both responses have the same equilibrium potential. Also, the receptors which react with the synaptic transmitter are desensitized by applied ACh. 5. Cholinesterase inhibitors (Tensilon and Eserine) have a variable action on different cells, with respect both to nerve-evoked and Ach evoked potentials. The reasons for this variation are unclear, and need further study. 6. Miniature e.p.s.p.s resemble analogous potentials at nerve-muscle junctions and other synapses. A significant proportion of the min e.p.s.p.s is released as multiple units. This proportion is increased in high Ca2+, while single units alone occur in a low Ca2+-high Mg2+ environment. 7. The experiments provide information about the release of ACh from nerve terminals and its action on the postsynaptic membrane of neurons. They are in good agreement with analogous studies on skeletal neuromuscular junctions

scholarly journals Rapid Mobilization of Membrane Lipids in Wheat Leaf Sheaths During Incompatible Interactions with Hessian Fly

2012 ◽  
Vol 25 (7) ◽  
pp. 920-930 ◽  
Author(s):  
Lieceng Zhu ◽  
Xuming Liu ◽  
Haiyan Wang ◽  
Chitvan Khajuria ◽  
John C. Reese ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Membrane Lipids ◽  
Hessian Fly ◽  
Delayed Response ◽  
Lipid Species ◽  
Polymerase Chain ◽  
Wheat Lines ◽  
Defense Molecules ◽  
Compatible Interactions ◽  
Incompatible Interactions

Hessian fly (HF) is a biotrophic insect that interacts with wheat on a gene-for-gene basis. We profiled changes in membrane lipids in two isogenic wheat lines: a susceptible line and its backcrossed offspring containing the resistance gene H13. Our results revealed a 32 to 45% reduction in total concentrations of 129 lipid species in resistant plants during incompatible interactions within 24 h after HF attack. A smaller and delayed response was observed in susceptible plants during compatible interactions. Microarray and real-time polymerase chain reaction analyses of 168 lipid-metabolism-related transcripts revealed that the abundance of many of these transcripts increased rapidly in resistant plants after HF attack but did not change in susceptible plants. In association with the rapid mobilization of membrane lipids, the concentrations of some fatty acids and 12-oxo-phytodienoic acid (OPDA) increased specifically in resistant plants. Exogenous application of OPDA increased mortality of HF larvae significantly. Collectively, our data, along with previously published results, indicate that the lipids were mobilized through lipolysis, producing free fatty acids, which were likely further converted into oxylipins and other defense molecules. Our results suggest that rapid mobilization of membrane lipids constitutes an important step for wheat to defend against HF attack.

scholarly journals Allostery revealed within lipid binding events to membrane proteins

2018 ◽  
Vol 115 (12) ◽  
pp. 2976-2981 ◽  
Author(s):  
John W. Patrick ◽  
Christopher D. Boone ◽  
Wen Liu ◽  
Gloria M. Conover ◽  
Yang Liu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Biological Membrane ◽  
Binding Constants ◽  
Native Mass Spectrometry ◽  
Specific Protein ◽  
Lipid Binding ◽  
Allosteric Modulation ◽  
Lipid Species ◽  
Specific Lipid

Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein−lipid assemblies. Despite this inherent complexity, the identification of specific protein−lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery [Monod J, Wyman J, Changeux JP (1965)J Mol Biol12:88–118]. Here, we use native mass spectrometry to determine the allosteric nature of heterogeneous lipid binding events to membrane proteins. We monitored individual lipid binding events to the ammonia channel (AmtB) fromEscherichia coli, enabling determination of their equilibrium binding constants. We found that different lipid pairs display a range of allosteric modulation. In particular, the binding of phosphatidylethanolamine and cardiolipin-like molecules to AmtB exhibited the largest degree of allosteric modulation, inspiring us to determine the cocrystal structure of AmtB in this lipid environment. The 2.45-Å resolution structure reveals a cardiolipin-like molecule bound to each subunit of the trimeric complex. Mutation of a single residue in AmtB abolishes the positive allosteric modulation observed for binding phosphatidylethanolamine and cardiolipin-like molecules. Our results demonstrate that specific lipid−protein interactions can act as allosteric modulators for the binding of different lipid types to integral membrane proteins.

scholarly journals Modeling Membrane Curvature Generation due to Membrane–Protein Interactions

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 120 ◽  
Author(s):  
Haleh Alimohamadi ◽  
Padmini Rangamani
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Current Model ◽  
Bilayer Membrane ◽  
Membrane Curvature ◽  
Elastic Membrane ◽  
Protein Distribution ◽  
Membrane Models ◽  
Generation Mechanisms ◽  
Mathematical And Computational Modeling

To alter and adjust the shape of the plasma membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the interactions between peripheral membrane proteins, integral membrane proteins, and lipids in the bilayer membrane. Mathematical and computational modeling of membrane curvature generation has provided great insights into the physics underlying these processes. However, one of the challenges in modeling these processes is identifying the suitable constitutive relationships that describe the membrane free energy including protein distribution and curvature generation capability. Here, we review some of the commonly used continuum elastic membrane models that have been developed for this purpose and discuss their applications. Finally, we address some fundamental challenges that future theoretical methods need to overcome to push the boundaries of current model applications.

scholarly journals Lipid-protein interactions are unique fingerprints for membrane proteins

2017 ◽  
Author(s):  
Valentina Corradi ◽  
Eduardo Mendez-Villuendas ◽  
Helgi I. Ingólfsson ◽  
Ruo-Xu Gu ◽  
Iwona Siuda ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Cell Membranes ◽  
Spatiotemporal Resolution ◽  
Lipid Dynamics ◽  
Lipid Species ◽  
Lipid Environment ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
Asymmetrically Distributed

ABSTRACTCell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.

scholarly journals Validation of MALDI-MS imaging data of selected membrane lipids in murine brain with and without laser postionization by quantitative nano-HPLC-MS using laser microdissection

2020 ◽  
Vol 412 (25) ◽  
pp. 6875-6886 ◽  
Author(s):  
Fabian B. Eiersbrock ◽  
Julian M. Orthen ◽  
Jens Soltwisch
Keyword(s):  
Signal Intensity ◽  
Laser Microdissection ◽  
Membrane Lipids ◽  
Chemical Properties ◽  
Small Sample ◽  
Tissue Type ◽  
Imaging Data ◽  
Response Factors ◽  
Lipid Species ◽  
Intensity Response

Abstract MALDI mass spectrometry imaging (MALDI-MSI) is a widely used technique to map the spatial distribution of molecules in sectioned tissue. The technique is based on the systematic generation and analysis of ions from small sample volumes, each representing a single pixel of the investigated sample surface. Subsequently, mass spectrometric images for any recorded ion species can be generated by displaying the signal intensity at the coordinate of origin for each of these pixels. Although easily equalized, these recorded signal intensities, however, are not necessarily a good measure for the underlying amount of analyte and care has to be taken in the interpretation of MALDI-MSI data. Physical and chemical properties that define the analyte molecules’ adjacencies in the tissue largely influence the local extraction and ionization efficiencies, possibly leading to strong variations in signal intensity response. Here, we inspect the validity of signal intensity distributions recorded from murine cerebellum as a measure for the underlying molar distributions. Based on segmentation derived from MALDI-MSI measurements, laser microdissection (LMD) was used to cut out regions of interest with a homogenous signal intensity. The molar concentration of six exemplary selected membrane lipids from different lipid classes in these tissue regions was determined using quantitative nano-HPLC-ESI-MS. Comparison of molar concentrations and signal intensity revealed strong deviations between underlying concentration and the distribution suggested by MSI data. Determined signal intensity response factors strongly depend on tissue type and lipid species.

High susceptibility to hypoxia of afferent synaptic transmission in the goldfish sacculus

1987 ◽  
Vol 58 (5) ◽  
pp. 1066-1079 ◽  
Author(s):  
T. Suzue ◽  
G. B. Wu ◽  
T. Furukawa
Keyword(s):  
Synaptic Transmission ◽  
Hair Cells ◽  
Afferent Fiber ◽  
Marked Change ◽  
Threshold Current ◽  
Postsynaptic Membrane ◽  
Afferent Fibers ◽  
Presynaptic Mechanisms ◽  
Binomial Parameter ◽  
Set Up

1. The effect of hypoxia on synaptic transmission between hair cells and afferent fibers was examined in the sacculus of goldfish. For this, we recorded potentials, intracellularly, from large afferent fibers. Anoxia was introduced by perfusing the gill with water deprived of oxygen or by halting the water flow to the gill. 2. The ear of the goldfish is most sensitive to hypoxia. Sound-evoked afferent activities were profoundly depressed within several minutes after the introduction of hypoxia. 3. The depressed afferent activity was attributed to a reduction in the amplitude of sound-evoked excitatory postsynaptic potentials (EPSPs) generated at afferent fiber terminals, since no significant change was detected in the resting and action potentials of afferent fibers or in intensity of the threshold current required to set up an action potential. Also, there was no marked change in the electrical activity of hair cells, determined by the finding that the amplitude of intramacularly recorded microphonic potentials and that of the coupling potentials was not altered. 4. A statistical analysis of the amplitude of sound-evoked EPSPs revealed that the binomial parameter n decreased during hypoxia, in parallel with a reduction in the amplitude of EPSPs, while the binomial parameter p either remained unaltered or was augmented. No change was found in the quantal size, thereby indicating that the sensitivity of the postsynaptic membrane remained unchanged. These results indicate that presynaptic mechanisms within hair cells, especially those playing a role in transmitter release or in replenishment of the latter, are suppressed during hypoxia.

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