scholarly journals Contacting domains that segregate lipid from solute transporters in malaria parasites

2019 ◽  
Author(s):  
Matthias Garten ◽  
Josh R. Beck ◽  
Robyn Roth ◽  
Tatyana Tenkova-Heuser ◽  
John Heuser ◽  
...  
Keyword(s):  
Parasitophorous Vacuole ◽  
Molecular Data ◽  
Cell Junctions ◽  
Transport Systems ◽  
Close Apposition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Intracellular Parasites ◽  
Intracellular Organelles ◽  
Membrane Contact

ABSTRACTWhile membrane contact sites (MCS) between intracellular organelles are abundant1, and cell-cell junctions are classically defined2, very little is known about the contacts between membranes that delimit extracellular junctions within cells, such as those of chloroplasts and intracellular parasites. The malaria parasite replicates within a unique organelle, the parasitophorous vacuole (PV) but the mechanism(s) are obscure by which the limiting membrane of the PV, the parasitophorous vacuolar membrane (PVM), collaborates with the parasite plasma membrane (PPM) to support the transport of proteins, lipids, nutrients, and metabolites between the cytoplasm of the parasite and the cytoplasm of the host erythrocyte (RBC). Here, we demonstrate the existence of multiple micrometer-sized regions of especially close apposition between the PVM and the PPM. To determine if these contact sites are involved in any sort of transport, we localized the PVM nutrient-permeable and protein export channel EXP2, as well as the PPM lipid transporter PfNCR1. We found that EXP2 is excluded from, but PfNCR1 is included within these regions of close apposition. Thus, these two different transport systems handling hydrophilic and hydrophobic substances, respectively, assume complementary and exclusive distributions. This new structural and molecular data assigns a functional significance to a macroscopic membrane domain.

Mitochondria–organelle contact sites: the plot thickens

2017 ◽  
Vol 45 (2) ◽  
pp. 477-488 ◽  
Author(s):  
Yael Elbaz-Alon
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Cellular Metabolism ◽  
Close Apposition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Cellular Organelles

Membrane contact sites (MCSs) are areas of close apposition between the membranes of two different organelles that enable non-vesicular transfer of ions and lipids. Recent studies reveal that mitochondria maintain contact sites with organelles other than the endoplasmic reticulum such as the vacuole, plasma membrane and peroxisomes. This review focuses on novel findings achieved mainly in yeast regarding tethers, function and regulation of mitochondria–organelle contact sites. The emerging network of MCSs linking virtually all cellular organelles is highly dynamic and integrated with cellular metabolism.

scholarly journals The Drosophila photoreceptor as a model system for studying signalling at membrane contact sites

2016 ◽  
Vol 44 (2) ◽  
pp. 447-451 ◽  
Author(s):  
Shweta Yadav ◽  
Shamshad Cockcroft ◽  
Padinjat Raghu
Keyword(s):  
Membrane Composition ◽  
Contact Site ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Physiological Processes ◽  
Specific Proteins ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Cellular Compartments

Several recent studies have demonstrated the existence of membrane contact sites (MCS) between intracellular organelles in eukaryotic cells. Recent exciting studies have also demonstrated the existence of biomolecular interactions at these contact sites in mediating changes in the membrane composition of the cellular compartments. However, the role of such contact sites in regulating organelle function and physiological processes remains less clear. In this review we discuss the existence of a contact site between the plasma membrane (PM) and the endoplasmic reticulum (ER) in Drosophila photoreceptors. Further, we discuss the role of specific proteins present at this location in regulating phospholipid turnover and its impact in regulating a physiological process, namely phototransduction.

scholarly journals Perspectives on Mitochondria–ER and Mitochondria–Lipid Droplet Contact in Hepatocytes and Hepatic Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2273
Author(s):  
Xiaowen Ma ◽  
Hui Qian ◽  
Allen Chen ◽  
Hong-Min Ni ◽  
Wen-Xing Ding
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Lipid Droplet ◽  
Alcoholic Fatty Liver ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Intracellular Organelles ◽  
Membrane Contact ◽  
Related Liver Disease ◽  
Organelle Communication

Emerging evidence suggests that mitochondrion–endoplasmic reticulum (ER) and mitochondrion–lipid droplet (LD) contact sites are critical in regulating lipid metabolism in cells. It is well established that intracellular organelles communicate with each other continuously through membrane contact sites to maintain organelle function and cellular homeostasis. The accumulation of LDs in hepatocytes is an early indicator of non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), which may indicate a breakdown in proper inter-organelle communication. In this review, we discuss previous findings in mitochondrion–ER and mitochondrion–LD contact, focusing on their roles in lipid metabolism in hepatocytes. We also present evidence of a unique mitochondrion–LD contact structure in hepatocytes under various physiological and pathological conditions and propose a working hypothesis to speculate about the role of these structures in regulating the functions of mitochondria and LDs and their implications in NAFLD and ALD.

scholarly journals The Interactome of the VAP Family of Proteins: An Overview

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1780
Author(s):  
Christina James ◽  
Ralph H. Kehlenbach
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Homeostasis ◽  
In Silico ◽  
Lipid Transport ◽  
Biological Processes ◽  
Close Apposition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Associated Proteins ◽  
Membrane Contact

Membrane contact sites (MCS) are sites of close apposition of two organelles that help in lipid transport and synthesis, calcium homeostasis and several other biological processes. The VAMP-associated proteins (VAPs) VAPA, VAPB, MOSPD2 and the recently described MOSPD1 and MOSPD3 are tether proteins of MCSs that are mainly found at the endoplasmic reticulum (ER). VAPs interact with various proteins with a motif called FFAT (two phenylalanines in an acidic tract), recruiting the associated organelle to the ER. In addition to the conventional FFAT motif, the recently described FFNT (two phenylalanines in a neutral tract) and phospho-FFAT motifs contribute to the interaction with VAPs. In this review, we summarize and compare the recent interactome studies described for VAPs, including in silico and proximity labeling methods. Collectively, the interaction repertoire of VAPs is very diverse and highlights the complexity of interactions mediated by the different FFAT motifs to the VAPs.

scholarly journals OSBP-mediated cholesterol transfer determines epithelial polarity and associated cargo secretion

2021 ◽  
Author(s):  
David Kovacs ◽  
Anne-Sophie Gay ◽  
Lucile Fleuriot ◽  
Delphine Debayle ◽  
Ana Rita Dias Araujo ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Lipid Transfer Protein ◽  
Cell Junctions ◽  
Lipid Transfer ◽  
Mesenchymal Transition ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Lipid Environment ◽  
E Cadherin

Golgi lipid environment regulates sorting and cargo secretion. However, the mechanisms that spatiotemporally control the lipid composition of the secretory membranes to drive cargo trafficking are poorly understood. Lipid transfer proteins regulate the concentration of specific lipids at membrane contact sites. We hypothesised that by catalysing cholesterol/PI(4)P exchange at ER-trans-Golgi membrane contact sites the lipid transfer protein oxysterol binding protein (OSBP) affects the secretion of a subset of cargoes. Here, we report that OSBP is a major epithelial protein as its inhibition leads to complete loss of apico-basal polarity. By mapping the OSBP proximity proteome with the biotin ligase TurboID, we found that OSBP controls the secretion of multiple membrane associated proteins, including key polarity determinants such as E-cadherin. Mechanistically, we established that OSBP contributes to E-cadherin secretion by supplying cholesterol to post-Golgi membranes. Importantly, when cells downregulate cell-cell junctions upon epithelial-to-mesenchymal transition, they re-wire their lipid homeostasis and downregulate OSBP as well, thus altering the trafficking of the OSBP-dependent secretory cargoes.

scholarly journals Bridging the gap: Membrane contact sites in signaling, metabolism, and organelle dynamics

2014 ◽  
Vol 205 (6) ◽  
pp. 759-769 ◽  
Author(s):  
William A. Prinz
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Intracellular Signaling ◽  
Close Apposition ◽  
Organelle Inheritance ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Regions of close apposition between two organelles, often referred to as membrane contact sites (MCSs), mostly form between the endoplasmic reticulum and a second organelle, although contacts between mitochondria and other organelles have also begun to be characterized. Although these contact sites have been noted since cells first began to be visualized with electron microscopy, the functions of most of these domains long remained unclear. The last few years have witnessed a dramatic increase in our understanding of MCSs, revealing the critical roles they play in intracellular signaling, metabolism, the trafficking of metabolites, and organelle inheritance, division, and transport.

scholarly journals Caenorhabditis elegans Junctophilin has tissue-specific functions and regulates neurotransmission with extended-synaptotagmin

Genetics ◽  
2021 ◽  
Author(s):  
Christopher A Piggott ◽  
Zilu Wu ◽  
Stephen Nurrish ◽  
Suhong Xu ◽  
Joshua M Kaplan ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Tissue Specific ◽  
Voltage Gated ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Pharyngeal Muscles ◽  
Membrane Contact ◽  
Null Mutants

Abstract The junctophilin family of proteins tether together plasma membrane (PM) and endoplasmic reticulum (ER) membranes, and couple PM- and ER-localized calcium channels. Understanding in vivo functions of junctophilins is of great interest for dissecting the physiological roles of ER-PM contact sites. Here, we show that the sole C. elegans junctophilin JPH-1 localizes to discrete membrane contact sites in neurons and muscles and has important tissue-specific functions. jph-1 null mutants display slow growth and development due to weaker contraction of pharyngeal muscles, leading to reduced feeding. In the body wall muscle, JPH-1 co-localizes with the PM-localized EGL-19 voltage-gated calcium channel and ER-localized UNC-68/RyR calcium channel, and is required for animal movement. In neurons, JPH-1 co-localizes with the membrane contact site protein Extended-SYnaptoTagmin 2 (ESYT-2) in soma, and is present near presynaptic release sites. Interestingly, jph-1 and esyt-2 null mutants display mutual suppression in their response to aldicarb, suggesting that JPH-1 and ESYT-2 have antagonistic roles in neuromuscular synaptic transmission. Additionally, we find an unexpected cell non-autonomous effect of jph-1 in axon regrowth after injury. Genetic double mutant analysis suggests that jph-1 functions in overlapping pathways with two PM-localized voltage-gated calcium channels, egl-19 and unc-2, and unc-68/RyR for animal health and development. Finally, we show that jph-1 regulates the colocalization of EGL-19 and UNC-68 and that unc-68/RyR is required for JPH-1 localization to ER-PM puncta. Our data demonstrate important roles for junctophilin in cellular physiology, and also provide insights into how junctophilin functions together with other calcium channels in vivo.

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