bims-mecosi Biomed News
on Membrane contact sites
Issue of 2022‒05‒29
seven papers selected by
Verena Kohler
  1. Cell death regulation by MAMs: from molecular mechanisms to therapeutic implications in cardiovascular diseases.
  2. Stable Integration of Inducible SPLICS Reporters Enables Spatio-Temporal Analysis of Multiple Organelle Contact Sites upon Modulation of Cholesterol Traffic.
  3. Multiple Ways to Keep FFAT Under Control!
  4. Phospholipid Membrane Transport and Associated Diseases.
  5. The ER ladder is a unique morphological feature of developing mammalian axons.
  6. Coordinated cortical ER remodeling facilitates actomyosin ring assembly.
  7. Defining ER-mitochondria contact dynamics in Plasmodium falciparum by targeting component of phospholipid synthesis pathway, Phosphatidylserine synthase (PfPSS).
  1. Cell Death Dis. 2022 May 27. 13(5): 504
    Cell death regulation by MAMs: from molecular mechanisms to therapeutic implications in cardiovascular diseases.
    Yiran E Li, James R Sowers, Claudio Hetz, Jun Ren.
      The endoplasmic reticulum (ER) and mitochondria are interconnected intracellular organelles with vital roles in the regulation of cell signaling and function. While the ER participates in a number of biological processes including lipid biosynthesis, Ca2+ storage and protein folding and processing, mitochondria are highly dynamic organelles governing ATP synthesis, free radical production, innate immunity and apoptosis. Interplay between the ER and mitochondria plays a crucial role in regulating energy metabolism and cell fate control under stress. The mitochondria-associated membranes (MAMs) denote physical contact sites between ER and mitochondria that mediate bidirectional communications between the two organelles. Although Ca2+ transport from ER to mitochondria is vital for mitochondrial homeostasis and energy metabolism, unrestrained Ca2+ transfer may result in mitochondrial Ca2+ overload, mitochondrial damage and cell death. Here we summarize the roles of MAMs in cell physiology and its impact in pathological conditions with a focus on cardiovascular disease. The possibility of manipulating ER-mitochondria contacts as potential therapeutic approaches is also discussed.
    DOI:  https://doi.org/10.1038/s41419-022-04942-2
  2. Cells. 2022 May 14. pii: 1643. [Epub ahead of print]11(10):
    Stable Integration of Inducible SPLICS Reporters Enables Spatio-Temporal Analysis of Multiple Organelle Contact Sites upon Modulation of Cholesterol Traffic.
    Flavia Giamogante, Lucia Barazzuol, Elena Poggio, Marta Tromboni, Marisa Brini, Tito Calì.
      The study of organelle contact sites has received a great impulse due to increased interest in the understanding of their involvement in many disease conditions. Split-GFP-based contact sites (SPLICS) reporters emerged as essential tools to easily detect changes in a wide range of organelle contact sites in cultured cells and in vivo, e.g., in zebrafish larvae. We report here on the generation of a new vector library of SPLICS cloned into a piggyBac system for stable and inducible expression of the reporters in a cell line of interest to overcome any potential weakness due to variable protein expression in transient transfection studies. Stable HeLa cell lines expressing SPLICS between the endoplasmic reticulum (ER) and mitochondria (MT), the ER and plasma membrane (PM), peroxisomes (PO) and ER, and PO and MT, were generated and tested for their ability to express the reporters upon treatment with doxycycline. Moreover, to take advantage of these cellular models, we decided to follow the behavior of different membrane contact sites upon modulating cholesterol traffic. Interestingly, we found that the acute pharmacological inhibition of the intracellular cholesterol transporter 1 (NPC1) differently affects membrane contact sites, highlighting the importance of different interfaces for cholesterol sensing and distribution within the cell.
    Keywords:  SPLICS; organelle contact sites; piggyBac system; split-GFP; stable cell lines
    DOI:  https://doi.org/10.3390/cells11101643
  3. Contact (Thousand Oaks). 2022 Jan 01. 5 1-4
    Multiple Ways to Keep FFAT Under Control!
    Suzan Kors, Michael Schrader, Joseph L Costello.
      Peroxisomes and the ER are closely inter-connected organelles, which collaborate in the metabolism of lipids. In a recent research paper in the Journal of Cell Biology, we describe a novel mechanism by which peroxisome-ER membrane contact sites are regulated, via phosphorylation of the peroxisomal protein ACBD5. We found that the interaction between ACBD5 and the ER protein VAPB, which we have previously shown to form a tether complex at peroxisome-ER contacts, is controlled by phosphorylation of ACBD5 at two different sites of its FFAT motif - the VAPB binding site. We also identify the kinase GSK3-β as being responsible for direct phosphorylation of ACBD5 to negatively regulate interaction with VAPB, leading to reduced peroxisome-ER contacts. In this article we provide additional insights into how this work, in combination with other studies on phosphorylation of VAP interactors, suggests a complex system of both positive and negative regulation of the FFAT motif via phosphorylation.
    Keywords:  ACBD5; ER; GSK3-β; PTPIP51; STARD3; VAPB; membrane contact sites; mitochondria; peroxisomes
    DOI:  https://doi.org/10.1177/25152564221101219
  4. Biomedicines. 2022 May 23. pii: 1201. [Epub ahead of print]10(5):
    Phospholipid Membrane Transport and Associated Diseases.
    Raúl Ventura, Inma Martínez-Ruiz, María Isabel Hernández-Alvarez.
      Phospholipids are the basic structure block of eukaryotic membranes, in both the outer and inner membranes, which delimit cell organelles. Phospholipids can also be damaged by oxidative stress produced by mitochondria, for instance, becoming oxidized phospholipids. These damaged phospholipids have been related to prevalent diseases such as atherosclerosis or non-alcoholic steatohepatitis (NASH) because they alter gene expression and induce cellular stress and apoptosis. One of the main sites of phospholipid synthesis is the endoplasmic reticulum (ER). ER association with other organelles through membrane contact sites (MCS) provides a close apposition for lipid transport. Additionally, an important advance in this small cytosolic gap are lipid transfer proteins (LTPs), which accelerate and modulate the distribution of phospholipids in other organelles. In this regard, LTPs can be established as an essential point within phospholipid circulation, as relevant data show impaired phospholipid transport when LTPs are defected. This review will focus on phospholipid function, metabolism, non-vesicular transport, and associated diseases.
    Keywords:  Mfn2; glycerophospholipid; lipid transport proteins; membrane contact sites; oxidized phospholipid
    DOI:  https://doi.org/10.3390/biomedicines10051201
  5. Dev Cell. 2022 May 17. pii: S1534-5807(22)00330-6. [Epub ahead of print]
    The ER ladder is a unique morphological feature of developing mammalian axons.
    Emiliano Zamponi, Janet B Meehl, Gia K Voeltz.
      The endoplasmic reticulum (ER) confronts a challenge to accommodate long, smooth ER tubules into the structural complexity of the axonal compartment. Here, we describe a morphological feature for the axonal ER network in developing neurons we termed the ER ladder. Axonal ER ladders are composed of rungs that wrap tightly around the microtubule bundle and dynamic rails, which slide across microtubules. We found that the ER-shaping protein Reticulon 2 determines the architecture and dynamics of the axonal ER ladder by modulating its interaction with microtubules. Moreover, we show that ER ladder depletion impairs the trafficking of associated vesicular axonal cargoes. Finally, we demonstrate that stromal interaction molecule 1 (Stim1) localizes to ER rungs and translocates to ER-plasma membrane contact sites upon depletion of luminal Ca2+. Our findings uncover fundamental insights into the structural and functional organization of the axonal ER network in developing mammalian neurons.
    Keywords:  axon development; cryo-ET; endoplasmic reticulum; microtubule bundle; neurodegeneration; organelle dynamics; organelle shape
    DOI:  https://doi.org/10.1016/j.devcel.2022.05.002
  6. Curr Biol. 2022 May 17. pii: S0960-9822(22)00722-9. [Epub ahead of print]
    Coordinated cortical ER remodeling facilitates actomyosin ring assembly.
    Dan Zhang, Tingyi See.
      The cortical endoplasmic reticulum (cER) is a reticulated network closely attached to the plasma membrane (PM). In the fission yeast Schizosaccharomyces pombe (S. pombe), ER-PM contacts have been suggested to restrict both the allocation and compaction of large-sized actomyosin assemblies along the lateral cell cortex. However, how cells orchestrate ER-PM contact remodeling in accordance with actomyosin coalescence for contractile ring assembly is unclear. Here, we reveal that actomyosin compaction directs the remodeling of the free tubular cER edges, whereas active exocytosis subsequently promotes the reorganization of the eisosome-bound cER rims by weakening their association or repatterning the eisosome-coated PM furrows. cER-eisosome contacts also act to reserve tubular cER edges and, hence, the ER shaping machinery at the lateral cell cortex. By manipulating or rerouting exocytosis in mutants with compromised actomyosin compaction, due to either the loss of myosin II activity or sheet-like cER morphology, we show that exocytosis facilitates ring formation likely by creating free tubular cER rims allowing robust cER remodeling. We thus propose that coordinated cER remodeling driven by both actomyosin forces and active exocytosis ensures proper contractile ring assembly. Our work also provides mechanistic insights into cER-related modulation in actomyosin ring assembly.
    Keywords:  ER-PM contact remodeling; ER-PM contacts; ER-eisosome contacts; VAP; actomyosin forces; actomyosin ring assembly; cER remodeling; eisosome; exocytosis; fission yeast
    DOI:  https://doi.org/10.1016/j.cub.2022.04.086
  7. Mitochondrion. 2022 May 24. pii: S1567-7249(22)00046-0. [Epub ahead of print]
    Defining ER-mitochondria contact dynamics in Plasmodium falciparum by targeting component of phospholipid synthesis pathway, Phosphatidylserine synthase (PfPSS).
    Omair Anwar, Muzahidul Islam, Vandana Thakur, Inderjeet Kaur, Asif Mohmmed.
      The malaria parasite completes the asexual cycle inside the host erythrocyte, which requires extensive membrane biogenesis for its development and multiplication. Metabolic pathways for the synthesis of membrane phospholipids (PL), including phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS), are crucial for parasite survival. Here, we have studied the P. falciparum enzyme responsible for PS synthesis, Phosphatidylserine synthase (PfPSS), GFP targeting approach confirmed it to be localized in the parasite ER as well as in ER-protrusions. Detailed high resolution microscopy, using these transgenic parasites expressing PfPSS-GFP, redefined the dynamics of ER during the intraerythrocytic life cycle and its association with the mitochondria. We report for the first time presence of ER-mitochondria contact (ERMC) in Plasmodium; ERMC is formed by PfPSS containing ER-protrusions, which associate with the mitochondria surface throughout the parasite growth cycle. Further, ERMC is found to be stable and refractory to ER and mitochondrial stresses, suggesting that it is formed through strong tethering complexes. PfPSS was found to interact with other major key enzyme involved in PL synthesis, choline/Etn-phosphotransferase (CEPT), which suggest that ER is the major site for PL biosynthesis. Overall, this study defines the morphological organisation of ERMC which mediates PL synthesis/transport in the Plasmodium.
    DOI:  https://doi.org/10.1016/j.mito.2022.05.005
This page is being maintained by Thomas Krichel. It was last updated on 2023‒10‒30 at 8:22.