scholarly journals Pex30-like proteins function as adaptors at distinct ER membrane contact sites

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Joana Veríssimo Ferreira ◽  
Pedro Carvalho
Keyword(s):  
Lipid Droplets ◽  
De Novo ◽  
Membrane Lipids ◽  
Family Members ◽  
Membrane Curvature ◽  
Organelle Biogenesis ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Er Membrane

Membrane lipids and proteins synthesized in the ER are used for de novo assembly of organelles, such as lipid droplets and peroxisomes. After assembly, the growth of these organelles is supported by ER-derived lipids transferred at membrane contact sites (MCSs). How ER sites for organelle biogenesis and lipid transfer are established and regulated is unclear. Here, we investigate how the ER membrane protein Pex30 and its family members Pex28, Pex29, Pex31, and Pex32 target and function at multiple MCSs. We show that different Pex30 complexes function at distinct ER domains and MCSs. Pex30 targets ER–peroxisome MCSs when bound to Pex28 and Pex32, organizes the nuclear–vacuolar junction when bound to Pex29, and promotes the biogenesis of lipid droplets independently of other family members. Importantly, the reticulon homology domain (RHD) mediates the assembly of the various Pex30 complexes. Given the role of RHD in membrane shaping, our findings offer a mechanistic link between MCS and regulation of membrane curvature.

scholarly journals Calcium signaling at ER membrane contact sites

2015 ◽  
Vol 1853 (9) ◽  
pp. 2012-2017 ◽  
Author(s):  
Thomas Burgoyne ◽  
Sandip Patel ◽  
Emily R. Eden
Keyword(s):  
Calcium Signaling ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Er Membrane

scholarly journals Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation

Science ◽  
2020 ◽  
Vol 369 (6508) ◽  
pp. eaaz7714 ◽  
Author(s):  
Justyna Sawa-Makarska ◽  
Verena Baumann ◽  
Nicolas Coudevylle ◽  
Sören von Bülow ◽  
Veronika Nogellova ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
De Novo ◽  
Lipid Transfer ◽  
Related Protein ◽  
Membrane Formation ◽  
Selective Autophagy ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Phosphatidylinositol 3

Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)–containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12–Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum.

scholarly journals Endoplasmic Reticulum‐Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling

2021 ◽  
Vol 22 (9) ◽  
pp. 4703
Author(s):  
Tim Crul ◽  
József Maléth
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Second Messengers ◽  
Adenosine Monophosphate ◽  
Camp Signaling ◽  
Cell Physiology ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Er Membrane

In eukaryotic cells, ultimate specificity in activation and action—for example, by means of second messengers—of the myriad of signaling cascades is primordial. In fact, versatile and ubiquitous second messengers, such as calcium (Ca2+) and cyclic adenosine monophosphate (cAMP), regulate multiple—sometimes opposite—cellular functions in a specific spatiotemporal manner. Cells achieve this through segregation of the initiators and modulators to specific plasma membrane (PM) subdomains, such as lipid rafts and caveolae, as well as by dynamic close contacts between the endoplasmic reticulum (ER) membrane and other intracellular organelles, including the PM. Especially, these membrane contact sites (MCSs) are currently receiving a lot of attention as their large influence on cell signaling regulation and cell physiology is increasingly appreciated. Depletion of ER Ca2+ stores activates ER membrane STIM proteins, which activate PM-residing Orai and TRPC Ca2+ channels at ER–PM contact sites. Within the MCS, Ca2+ fluxes relay to cAMP signaling through highly interconnected networks. However, the precise mechanisms of MCS formation and the influence of their dynamic lipid environment on their functional maintenance are not completely understood. The current review aims to provide an overview of our current understanding and to identify open questions of the field.

scholarly journals Peroxisomal Membrane Contact Sites in Yeasts

2021 ◽  
Vol 9 ◽  
Author(s):  
Amit S. Joshi
Keyword(s):  
Lipid Droplets ◽  
Peroxisome Biogenesis ◽  
Functional Importance ◽  
Peroxisomal Membrane ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Recent Developments ◽  
Membrane Contacts ◽  
Membrane Bound ◽  
Membrane Contact

Peroxisomes are ubiquitous, single membrane-bound organelles that play a crucial role in lipid metabolism and human health. While peroxisome number is maintained by the division of existing peroxisomes, nascent peroxisomes can be generated from the endoplasmic reticulum (ER) membrane in yeasts. During formation and proliferation, peroxisomes maintain membrane contacts with the ER. In addition to the ER, contacts between peroxisomes and other organelles such as lipid droplets, mitochondria, vacuole, and plasma membrane have been reported. These membrane contact sites (MCS) are dynamic and important for cellular function. This review focuses on the recent developments in peroxisome biogenesis and the functional importance of peroxisomal MCS in yeasts.

scholarly journals In-vitro Reconstitution of Membrane Contact Sites between the Endoplasmic Reticulum and Lipid Droplets

2021 ◽  
Author(s):  
Sukrut Kamerkar ◽  
Jagjeet Singh ◽  
Subham Tripathy ◽  
Hemangi Bhonsle ◽  
Mukesh Kumar ◽  
...  
Keyword(s):  
Rat Liver ◽  
Lipid Droplets ◽  
Cell Function ◽  
Cultured Cells ◽  
Optical Trap ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Organelle Communication

Coordinated cell function requires inter-organelle communication across Membrane Contact Sites (MCS). Here we deposit ER-enriched microsomes purified from rat liver or from cultured cells on a coverslip in the form of a continuous planar membrane. We visualize real-time protein and lipid exchanges across MCS that form between this ER-mimicking membrane and lipid droplets purified from rat liver. An Optical trap is used to demonstrate physical tethering of individual lipid droplets to the ER-mimicking membrane at MCS, and to directly measure the strength of this tether. In-vitro MCS formation changes dramatically in response to metabolic state and immune activation in the animal. Surprisingly, we find that the Rab18 GTPase and Phosphatidic acid are common molecular factors to control both of these pathways. This assay could possibly be adapted to interrogate MCS formation between other membranes (e.g. mitochondria, peroxisomes, endosomes etc.), and abnormalities therein that cause neurological, metabolic and pathogenic diseases.

scholarly journals Here, there, and everywhere: The importance of ER membrane contact sites

Science ◽  
2018 ◽  
Vol 361 (6401) ◽  
pp. eaan5835 ◽  
Author(s):  
Haoxi Wu ◽  
Pedro Carvalho ◽  
Gia K. Voeltz
Keyword(s):  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
Er Membrane

scholarly journals Getting a handle on lipid droplets: Insights into ER–lipid droplet tethering

2019 ◽  
Vol 218 (4) ◽  
pp. 1089-1091 ◽  
Author(s):  
Truc B. Nguyen ◽  
James A. Olzmann
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Human Cells ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Cell Biol ◽  
Membrane Contact

Lipid droplets (LDs) are hubs for lipid metabolism that form membrane contact sites with multiple organelles. In this issue, Hariri et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808119) reveal the functions of Mdm1-mediated endoplasmic reticulum (ER)–LD tethering in yeast and Datta et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201808133) identify a role for the Mdm1 orthologue, Snx14, as an ER–LD tether that regulates lipid metabolism in human cells.

scholarly journals Membrane Contact Sites in Yeast: Control Hubs of Sphingolipid Homeostasis

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 971
Author(s):  
Philipp Schlarmann ◽  
Atsuko Ikeda ◽  
Kouichi Funato
Keyword(s):  
Plasma Membrane ◽  
Intracellular Signaling ◽  
Membrane Lipids ◽  
Sphingolipid Metabolism ◽  
Yeast Saccharomyces Cerevisiae ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact ◽  
And Function

Sphingolipids are the most diverse class of membrane lipids, in terms of their structure and function. Structurally simple sphingolipid precursors, such as ceramides, act as intracellular signaling molecules in various processes, including apoptosis, whereas mature and complex forms of sphingolipids are important structural components of the plasma membrane. Supplying complex sphingolipids to the plasma membrane, according to need, while keeping pro-apoptotic ceramides in check is an intricate task for the cell and requires mechanisms that tightly control sphingolipid synthesis, breakdown, and storage. As each of these processes takes place in different organelles, recent studies, using the budding yeast Saccharomyces cerevisiae, have investigated the role of membrane contact sites as hubs that integrate inter-organellar sphingolipid transport and regulation. In this review, we provide a detailed overview of the findings of these studies and put them into the context of established regulatory mechanisms of sphingolipid homeostasis. We have focused on the role of membrane contact sites in sphingolipid metabolism and ceramide transport, as well as the mechanisms that prevent toxic ceramide accumulation.

scholarly journals ORP5 AND ORP8 ORCHESTRATE LIPID DROPLET BIOGENESIS AND MAINTENANCE AT ER-MITOCHONDRIA CONTACT SITES

2021 ◽  
Author(s):  
Valentin Guyard ◽  
Vera F Monteiro-Cardoso ◽  
Mohyeddine Omrane ◽  
Cecile Sauvanet ◽  
Audrey Houcine ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Phosphatidic Acid ◽  
Lipid Droplets ◽  
Neutral Lipids ◽  
Nucleation And Growth ◽  
Lipid Transfer ◽  
Lipid Transfer Proteins ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Membrane Contact

Lipid droplets (LDs) are the primary organelles of lipid storage, buffering energy fluctuations of the cell. They store neutral lipids in their core that is surrounded by a protein-decorated phospholipid monolayer. LDs arise from the Endoplasmic Reticulum (ER). The ER-protein seipin, localizing at ER-LD junctions, controls LD nucleation and growth. However, how LD biogenesis is spatially and temporally coordinated remains elusive. Here, we show that the lipid transfer proteins ORP5 and ORP8 control LD biogenesis at Mitochondria-Associated ER Membrane (MAM) subdomains, enriched in phosphatidic acid. We found that ORP5/8 regulate seipin recruitment to these MAM-LD contacts, and their loss impairs LD biogenesis. Importantly, the integrity of ER-mitochondria contact sites is crucial for the ORP5/8 function in regulating seipin-mediated LD biogenesis. Our study uncovers an unprecedented ORP5/8 role in orchestrating LD biogenesis at MAMs and brings novel insights into the metabolic crosstalk between mitochondria, ER, and LDs at membrane contact sites.

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