Cover: Artistic interpretation of protein N-glycosylation, a process that occurs in the endoplasmic reticulum (ER) and involves the transfer of a glycan, Glc3Man9GlcNAc2, from a dolichol diphosphate lipid carrier to a nascent polypeptide in the ER lumen. The image depicts the ER membrane (ER lumen above and the cytosol below) with, from right to left, the translocon-associated protein (TRAP), Sec61, the oligosaccharyltransferase and a dolichol diphosphate molecule bound to a glycan. Artwork by Ayelen Valko, using a mixed technique involving collage, acrylic painting and digital processing. See article by G. L. Gallo, A. Valko et al. (jcs259167).
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Special Issue: Cell Biology of Lipids
CELL SCIENTISTS TO WATCH
CELL SCIENCE AT A GLANCE
Perilipins at a glance
Summary: Perilipins coat lipid droplets to regulate their metabolism and signaling, influencing disease development.
Lipophagy at a glance
Summary: This Cell Science at a Glance article and accompanying poster provides an overview of the cellular mechanisms governing lipophagy in yeast and mammals.
A possible role for VPS13-family proteins in bulk lipid transfer, membrane expansion and organelle biogenesis
Summary: We discuss emerging roles of VPS13-family proteins in vesicle-independent bulk lipid transport between organelles, the possible functions of such transport and the underlying molecular mechanisms.
Nuclear lipid droplets – how are they different from their cytoplasmic siblings?
Summary: Lipid droplets in the nucleus form through pathways that are different from those of their cytoplasmic counterparts and appear to have unique functions, but many questions remain to be addressed, as reviewed here.
Dissecting lipid droplet biology with coherent Raman scattering microscopy
Summary: Coherent Raman scattering microscopy offers label-free imaging of lipid droplets with chemical specificity. Here, we discuss the recent advancement in the field.
Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport
Summary: Transport of lipids across vessel walls is vital for tissue function. We show that adipocytes regulate this process by paracrine secretion of lactate, linking carbohydrate metabolism to control of fat influx.
S-acylation of Orai1 regulates store-operated Ca2+ entry
Summary: Dynamic S-acylation of Ca2+ release-activated channel Orai1 is required for its recruitment to the plasma membrane subdomains and subsequent activation.
Lipid-driven CFTR clustering is impaired in cystic fibrosis and restored by corrector drugs
Summary: CFTR clustering in ceramide-rich platforms is independent of protein–protein interactions, driven by lipid phase separation, prevented by CFTR mutations that cause misfolding and restored by Trikafta correctors.
ADAR1 inhibits adipogenesis and obesity by interacting with Dicer to promote the maturation of miR-155-5P
Summary: ADAR1 acts as an inhibitor of adipogenesis via enhanced production of miR-155-5p and downregulating the adipogenic early transcription factor C/EBPα.
Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification
Summary: Changing neutral sphingomyelinase 2 activity regulates small extracellular vesicle secretion through modulation of V-ATPase activity.
DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics
Summary: An increase in DHA-containing phospholipids induces higher fusion events triggered by toxin-mediated RhoA inhibition. The cells respond back by rapidly regulating the overall transendothelial macroaperture surface area.
Analysis of sex-specific lipid metabolism of Plasmodium falciparum points to the importance of sphingomyelin for gametocytogenesis
Summary: The lipids of human red blood cells infected with Plasmodium falciparum are indicative of parasite life cycle stage and sex. Sphingolipids are distributed in a sex-specific manner and are important for gametocyte viability.
A novel fission yeast platform to model N-glycosylation and the bases of congenital disorders of glycosylation type I
Summary: We use a new set of Schizosaccharomyces pombe mutants to explore the molecular bases of lipid-linked oligosaccharide synthesis and N-glycosylation involved in congenital disorders of glycosylation type I
Dishevelled coordinates phosphoinositide kinases PI4KIIIα and PIP5KIγ for efficient PtdInsP2 synthesis
Summary: Efficient synthesis of the membrane phospholipid PtdIns(4,5)P2 from PtdIns depends on expression of the scaffolding protein Dvl3, which dynamically couples lipid kinases PI4KIIIα and PIP5KIγ.
HDLs extract lipophilic drugs from cells
Summary: HDLs, akin to their capacity for extracting cholesterol, can remove lipophilic compounds from cells, thus protecting the cells when these compounds are toxic.
Snazarus and its human ortholog SNX25 modulate autophagic flux
Summary: There is a functional and conserved requirement for Drosophila Snazarus and its human ortholog sorting nexin 25 in autophagy. They modulate endocytosis and lipid homeostasis via specific domains.
The endoplasmic reticulum–plasma membrane tethering protein TMEM24 is a regulator of cellular Ca2+ homeostasis
Summary: TMEM24 reversibly localizes to ER–PM contact sites and participates in the regulation of both ER and mitochondrial Ca2+ homeostasis and in glucose-dependent ATP production in insulin-secreting cells.
Apolipoprotein A1 deficiency in mice primes bone marrow stem cells for T cell lymphopoiesis
Summary: Changes in cholesterol metabolism, that is, in high-density lipoprotein levels, can significantly impact leukocyte numbers via modulating bone marrow functionality.
Co-translational biogenesis of lipid droplet integral membrane proteins
Summary: Insertion of many lipid droplet membrane proteins into the ER is co-translational, mediated by the ER membrane protein complex and may involve topology reorientation.
A three-organelle complex made by wrappER contacts with peroxisomes and mitochondria responds to liver lipid flux changes
Summary: In liver hepatocytes, the wrappER, a wrapping type of rough ER, simultaneously connects mitochondria and peroxisomes to form a three-organelle complex that responds to changes in hepatic lipid flux.
A palmitoylation code controls PI4KIIIα complex formation and PI(4,5)P2 homeostasis at the plasma membrane
Summary: Different palmitoylation patterns on a lipid kinase adaptor protein control partitioning of the kinase between two spatiotemporally and functionally distinct complexes within the plasma membrane.
Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis
Summary: A product of cholesterol ester oxidation that is found in plasma of cardiovascular disease patients induces lysosome stress, culminating with the formation of vascular smooth muscle foam cells.
CDC50A is required for aminophospholipid transport and cell fusion in mouse C2C12 myoblasts
Summary: Myoblasts exhibit an aminophospholipid flippase activity that relies on CDC50A-dependent P4-ATPases. Loss of CDC50A compromises actin remodeling, RAC1 membrane targeting and cell fusion.
S-palmitoylation determines TMEM55B-dependent positioning of lysosomes
Summary: TMEM55B mediates the transport of lysosomes. We show that TMEM55B undergoes S-palmitoylation at multiple cysteine residues to mediate transport of TMEM55B from the Golgi to lysosomes.
The Hob proteins are novel and conserved lipid-binding proteins at ER–PM contact sites
Summary: Membrane contact sites between organelles are critical regulators of cellular function. Here we identify the highly conserved Hob proteins as novel lipid-binding proteins at ER–PM contact sites.
Conserved cholesterol-related activities of Dispatched 1 drive Sonic hedgehog shedding from the cell membrane
Summary: The resistance–nodulation–division protein Dispatched 1 expels plasma membrane cholesterol to indirectly increase Sonic hedgehog morphogen release from the cell surface.
Characterization of lipoprotein lipase storage vesicles in 3T3-L1 adipocytes
Summary: Lipoprotein lipase is localized to large caveolar microdomains in 3T3-L1 adipocytes. In these cells, insulin regulates LPL secretion by driving trafficking of these domains via an ARF1-dependent mechanism.
Large organellar changes occur during mild heat shock in yeast
Summary: Exposure to mild heat shock leads to large quantifiable changes in the cellular ultrastructure of yeast, showing the involvement of multivesicular bodies in the heat-shock response and the apparition of novel structures.
Lipid droplets form a network interconnected by the endoplasmic reticulum through which their proteins equilibrate
Summary: A yeast mating-based microscopic readout is used to monitor the relocalization of lipid droplet proteins. LD proteins of the two mating partners quickly re-equilibrate their localization resulting in a uniform LD population.
Ca2+-dependent protein acyltransferase DHHC21 controls activation of CD4+ T cells
Summary: The acyltransferase DHHC21 is a novel component of the TCR signaling pathway that critically regulates activation and differentiation of CD4+ T cells by mediating rapid TCR-induced S-acylation of signaling proteins.
The surface of lipid droplets constitutes a barrier for endoplasmic reticulum-resident integral membrane proteins
Summary: The junction between the ER membrane and lipid droplets constitutes a barrier for the transfer of ER-resident membrane-spanning proteins to the surface of lipid droplets.
INPP5E controls ciliary localization of phospholipids and the odor response in olfactory sensory neurons
Summary: Cilia of olfactory sensory neurons have a unique lipid composition. Localization of phospholipids is controlled by the INPP5E phosphatase and is involved in modulation of the odor response.
Characterization of micron-scale protein-depleted plasma membrane domains in phosphatidylserine-deficient yeast cells
Summary: Yeast cells lacking phosphatidylserine generate protein-depleted plasma membrane domains, and vacuoles contact this domain. This is the first report of micron-scale plasma membrane domains in living cells.
PDZD8-mediated lipid transfer at contacts between the ER and late endosomes/lysosomes is required for neurite outgrowth
Summary: The synaptotagmin-like mitochondrial-lipid-binding domain of PDZD8 transports phospholipids and ceramides at ER-late endosome/lysosome (LE/lys) contacts to promote LE/lys positioning and neurite outgrowth.
Septins coordinate cell wall integrity and lipid metabolism in a sphingolipid-dependent process
Summary: Septins are critical for cell shape. Using mutants and agents that disturb cell walls and membranes, we show that septins are involved in lipid metabolism and cell wall integrity signaling.
Ferroptosis induces membrane blebbing in placental trophoblasts
Summary: Ferroptosis, a unique form of lipotoxic cell death, is associated with macro-blebbing of trophoblast plasma membranes, likely representing thinning and enhanced membrane flexibility during cell death-associated swelling.
TOOLS AND RESOURCES
Intracellular flow cytometric lipid analysis – a multiparametric system to assess distinct lipid classes in live cells
Summary: The lipophilic probes Nile Blue and Nile Red detect intracellular unsaturated free fatty acids and neutral lipids, respectively, and can be used for multiparametric imaging and flow cytometry.
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