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  1. Article ; Online: An extracellular vesicle targeting ligand that binds to Arc proteins and facilitates Arc transport in vivo.

    Lee, Peter H / Anaya, Michael / Ladinsky, Mark S / Reitsma, Justin M / Zinn, Kai

    eLife

    2023  Volume 12

    Abstract: Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are targeted to specific cell types. Here, we identify ... ...

    Abstract Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are targeted to specific cell types. Here, we identify the
    MeSH term(s) Animals ; Ligands ; Extracellular Vesicles/metabolism ; Drosophila/genetics ; Membrane Proteins/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; RNA, Messenger/metabolism ; Mammals/genetics
    Chemical Substances Ligands ; Membrane Proteins ; Drosophila Proteins ; RNA, Messenger
    Language English
    Publishing date 2023-06-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.82874
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Serial Cryomicrotomy of

    Ng, Cai Tong / Ladinsky, Mark S / Gan, Lu

    Bio-protocol

    2020  Volume 10, Issue 22, Page(s) e3831

    Abstract: Electron cryotomography (cryo-ET) is an increasingly popular technique to study cellular structures and ... ...

    Abstract Electron cryotomography (cryo-ET) is an increasingly popular technique to study cellular structures and macromolecules
    Language English
    Publishing date 2020-11-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325 ; 2331-8325
    ISSN (online) 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.3831
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Organellar Contacts of Milk Lipid Droplets.

    Monks, Jenifer / Ladinsky, Mark S / McManaman, James L

    Contact (Thousand Oaks (Ventura County, Calif.))

    2020  Volume 3

    Abstract: Milk-secreting epithelial cells of the mammary gland are functionally specialized for the synthesis and secretion of large quantities of neutral lipids, a major macronutrient in milk from most mammals. Milk lipid synthesis and secretion are hormonally ... ...

    Abstract Milk-secreting epithelial cells of the mammary gland are functionally specialized for the synthesis and secretion of large quantities of neutral lipids, a major macronutrient in milk from most mammals. Milk lipid synthesis and secretion are hormonally regulated and secretion occurs by a unique apocrine mechanism. Neutral lipids are synthesized and packaged into perilipin-2 (PLIN2) coated cytoplasmic lipid droplets within specialized cisternal domains of rough endoplasmic reticulum (ER). Continued lipid synthesis by ER membrane enzymes and lipid droplet fusion contribute to the large size of these cytoplasmic lipid droplets (5-15 μm in diameter). Lipid droplets are directionally trafficked within the epithelial cell to the apical plasma membrane. Upon contact, a molecular docking complex assembles to tether the droplet to the plasma membrane and facilitate its membrane envelopment. This docking complex consists of the transmembrane protein, butyrophilin, the cytoplasmic housekeeping protein, xanthine dehydrogenase/oxidoreductase, the lipid droplet coat proteins, PLIN2, and cell death-inducing DFFA-like effector A. Interactions of mitochondria, Golgi, and secretory vesicles with docked lipid droplets have also been reported and may supply membrane phospholipids, energy, or scaffold cytoskeleton for apocrine secretion of the lipid droplet. Final secretion of lipid droplets into the milk occurs in response to oxytocin-stimulated contraction of myoepithelial cells that surround milk-secreting epithelial cells. The mechanistic details of lipid droplet release are unknown at this time. The final secreted milk fat globule consists of a triglyceride core coated with a phospholipid monolayer and various coat proteins, fully encased in a membrane bilayer.
    Language English
    Publishing date 2020-01-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2964312-0
    ISSN 2515-2564 ; 2515-2564
    ISSN (online) 2515-2564
    ISSN 2515-2564
    DOI 10.1177/2515256419897226
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics.

    Sherman, David J / Liu, Lei / Mamrosh, Jennifer L / Xie, Jiansong / Ferbas, John / Lomenick, Brett / Ladinsky, Mark S / Verma, Rati / Rulifson, Ingrid C / Deshaies, Raymond J

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 18, Page(s) e2318619121

    Abstract: Nonalcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. ...

    Abstract Nonalcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene
    MeSH term(s) Humans ; Acyltransferases/metabolism ; Golgi Apparatus/metabolism ; Lipase/metabolism ; Lipase/genetics ; Lipid Droplets/metabolism ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Non-alcoholic Fatty Liver Disease/genetics ; Non-alcoholic Fatty Liver Disease/metabolism ; Non-alcoholic Fatty Liver Disease/pathology ; Phospholipases A2, Calcium-Independent/metabolism
    Chemical Substances Acyltransferases (EC 2.3.-) ; Lipase (EC 3.1.1.3) ; Membrane Proteins ; Phospholipases A2, Calcium-Independent (EC 3.1.1.4) ; PNPLA3 protein, human (EC 3.1.1.3)
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2318619121
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Micromanipulator-assisted vitreous cryosectioning and sample preparation by high-pressure freezing.

    Ladinsky, Mark S

    Methods in enzymology

    2010  Volume 481, Page(s) 165–194

    Abstract: Cryo-electron microscopy (cryo-EM) of unfixed, unstained, frozen-hydrated samples conveys the most reliable view of the "live" state of cells and tissues. Advances in sample preparation methods and electron microscope technology over the last decade have ...

    Abstract Cryo-electron microscopy (cryo-EM) of unfixed, unstained, frozen-hydrated samples conveys the most reliable view of the "live" state of cells and tissues. Advances in sample preparation methods and electron microscope technology over the last decade have made this approach more routine and available to a broader segment of the structural biology community. Many cryo-EM samples are thin enough to be imaged as wholemounts, but most cells and tissues are too thick and must be cryosectioned to obtain samples that are sufficiently thin for successful imaging. Cryosectioning of vitreous material is a challenging and time-consuming task. A number of laboratories have worked hard to develop approaches and technologies for cryosectioning and to carefully characterize the nature of vitreous sections and the artifacts associated with them. Several different cryosectioning methods are in use in cryo-EM laboratories, each of which is effective and routinely yields high-quality structural data. Here, we describe a particular method that utilizes a micromanipulator to aid the cryomicrotomist in controlling vitreous sections as they are being cut and to facilitate transfer of the sections to an EM grid. Each step in the process, from preparing samples by high-pressure freezing to affixing vitreous sections to a grid, is covered in detail, including discussions of cryosectioning hardware, environmental conditions, and sectioning artifacts.
    MeSH term(s) Cryoelectron Microscopy/methods ; Cryoultramicrotomy/methods ; Freezing ; Pressure
    Language English
    Publishing date 2010
    Publishing country United States
    Document type Journal Article
    ISSN 1557-7988 ; 0076-6879
    ISSN (online) 1557-7988
    ISSN 0076-6879
    DOI 10.1016/S0076-6879(10)81008-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Mitochondrial fission factor (Mff) is required for organization of the mitochondrial sheath in spermatids

    Varuzhanyan, Grigor / Chen, Hsiuchen / Rojansky, Rebecca / Ladinsky, Mark S / McCaffery, J. Michael / Chan, David C

    Biochimica et biophysica acta. 2021 May, v. 1865, no. 5

    2021  

    Abstract: Mitochondrial fission counterbalances fusion to maintain organelle morphology, but its role during development remains poorly characterized. Mammalian spermatogenesis is a complex developmental process involving several drastic changes to mitochondrial ... ...

    Abstract Mitochondrial fission counterbalances fusion to maintain organelle morphology, but its role during development remains poorly characterized. Mammalian spermatogenesis is a complex developmental process involving several drastic changes to mitochondrial shape and organization. Mitochondria are generally small and spherical in spermatogonia, elongate during meiosis, and fragment in haploid round spermatids. Near the end of spermatid maturation, small mitochondrial spheres line the axoneme, elongate, and tightly wrap around the midpiece to form the mitochondrial sheath, which is critical for fueling flagellar movements. It remains unclear how these changes in mitochondrial morphology are regulated and how they affect sperm development.We used genetic ablation of Mff (mitochondrial fission factor) in mice to investigate the role of mitochondrial fission during mammalian spermatogenesis.Our analysis indicates that Mff is required for mitochondrial fragmentation in haploid round spermatids and for organizing mitochondria in the midpiece in elongating spermatids. In Mff mutant mice, round spermatids have aberrantly elongated mitochondria that often show central constrictions, suggestive of failed fission events. In elongating spermatids and spermatozoa, mitochondrial sheaths are disjointed, containing swollen mitochondria with large gaps between organelles. These mitochondrial abnormalities in Mff mutant sperm are associated with reduced respiratory chain Complex IV activity, aberrant sperm morphology and motility, and reduced fertility.Mff is required for organization of the mitochondrial sheath in mouse sperm.Mitochondrial fission plays an important role in regulating mitochondrial organization during a complex developmental process.
    Keywords electron transport chain ; haploidy ; meiosis ; mice ; mitochondria ; mutants ; shape ; spermatids ; spermatogenesis ; spermatogonia ; spermatozoa
    Language English
    Dates of publication 2021-05
    Publishing place Elsevier B.V.
    Document type Article
    Note NAL-light
    ZDB-ID 840755-1
    ISSN 0304-4165
    ISSN 0304-4165
    DOI 10.1016/j.bbagen.2021.129845
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Uc I Zs.247: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  7. Article: Perilipin-2 promotes lipid droplet-plasma membrane interactions that facilitate apocrine lipid secretion in secretory epithelial cells of the mouse mammary gland.

    Monks, Jenifer / Orlicky, David J / Libby, Andrew E / Dzieciatkowska, Monica / Ladinsky, Mark S / McManaman, James L

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 958566

    Abstract: Secretory epithelial cells (sMEC) in mammary glands of lactating animals secrete lipids by a novel apocrine mechanism in which cytoplasmic lipid droplets (LD) contact and are enveloped by elements of the apical plasma membrane (APM) before being released ...

    Abstract Secretory epithelial cells (sMEC) in mammary glands of lactating animals secrete lipids by a novel apocrine mechanism in which cytoplasmic lipid droplets (LD) contact and are enveloped by elements of the apical plasma membrane (APM) before being released into the lumen of the gland as membrane bound structures. The molecular properties of LD-APM contacts and the mechanisms regulating LD membrane envelopment and secretion are not fully understood. Perilipin-2 (Plin2) is a constitutive LD protein that has been proposed to tether LD to the APM through formation of a complex with the transmembrane protein, butyrophilin1a1 (BTN) and the redox enzyme, xanthine oxidoreductase (XOR). Using mice lacking Plin2 and physiological inhibition of apocrine lipid secretion, we demonstrate that LD-APM contact and envelopment are mechanistically distinct steps that they are differentially regulated by Plin2 and independent of LD secretion. We find that Plin2 is not required for formation of LD-APM contacts. However, it increases the percentage of LD that contact the APM and mediates enlargement of the LD-APM contact zone as LD undergo membrane envelopment. The effects of Plin2 LD-APM interactions are associated with increased abundances of BTN, XOR and Cidea, which are implicated as mediators of LD-APM contact formation, on membranes surrounding secreted LD, and with promotion of glycocalyx remodeling at LD-APM contact sites. We propose that Plin2 does not directly mediate contact between LD and the APM but acts by enhancing molecular interactions that stabilize LD-APM contacts and govern membrane envelopment of LD during apocrine lipid secretion. Plin2 does not appear to significantly affect the lipid content of milk in fully lactating animals, but it does increase lipid secretion at the onset of lactation in primaparous dams, which suggest a role in facilitating apocrine lipid secretion in sMEC during their initial transition to a secretory phenotype.
    Language English
    Publishing date 2022-09-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.958566
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  8. Article: The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics.

    Sherman, David J / Liu, Lei / Mamrosh, Jennifer L / Xie, Jiansong / Ferbas, John / Lomenick, Brett / Ladinsky, Mark S / Verma, Rati / Rulifson, Ingrid C / Deshaies, Raymond J

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis ... ...

    Abstract Non-alcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a progressive metabolic disorder that begins with aberrant triglyceride accumulation in the liver and can lead to cirrhosis and cancer. A common variant in the gene
    Language English
    Publishing date 2023-10-14
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.13.562302
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Multiscale Imaging of HIV-1 Transmission in Humanized Mice.

    Kieffer, Collin / Ladinsky, Mark S / Bjorkman, Pamela J

    AIDS research and human retroviruses

    2017  Volume 33, Issue S1, Page(s) S6–S7

    MeSH term(s) Animals ; Electron Microscope Tomography ; Fluorescent Antibody Technique ; HIV Infections/diagnostic imaging ; HIV Infections/pathology ; HIV Infections/transmission ; HIV Infections/virology ; HIV-1/growth & development ; Imaging, Three-Dimensional ; Longitudinal Studies ; Lymphoid Tissue/pathology ; Lymphoid Tissue/virology ; Mice, SCID ; Virion/metabolism ; Virion/ultrastructure
    Language English
    Publishing date 2017-12-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/AID.2017.0142
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1928: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  10. Article ; Online: The Evolution of Interdependence in a Four-Way Mealybug Symbiosis.

    Garber, Arkadiy I / Kupper, Maria / Laetsch, Dominik R / Weldon, Stephanie R / Ladinsky, Mark S / Bjorkman, Pamela J / McCutcheon, John P

    Genome biology and evolution

    2021  Volume 13, Issue 8

    Abstract: Mealybugs are insects that maintain intracellular bacterial symbionts to supplement their nutrient-poor plant sap diets. Some mealybugs have a single betaproteobacterial endosymbiont, a Candidatus Tremblaya species (hereafter Tremblaya) that alone ... ...

    Abstract Mealybugs are insects that maintain intracellular bacterial symbionts to supplement their nutrient-poor plant sap diets. Some mealybugs have a single betaproteobacterial endosymbiont, a Candidatus Tremblaya species (hereafter Tremblaya) that alone provides the insect with its required nutrients. Other mealybugs have two nutritional endosymbionts that together provision these same nutrients, where Tremblaya has gained a gammaproteobacterial partner that resides in its cytoplasm. Previous work had established that Pseudococcus longispinus mealybugs maintain not one but two species of gammaproteobacterial endosymbionts along with Tremblaya. Preliminary genomic analyses suggested that these two gammaproteobacterial endosymbionts have large genomes with features consistent with a relatively recent origin as insect endosymbionts, but the patterns of genomic complementarity between members of the symbiosis and their relative cellular locations were unknown. Here, using long-read sequencing and various types of microscopy, we show that the two gammaproteobacterial symbionts of P. longispinus are mixed together within Tremblaya cells, and that their genomes are somewhat reduced in size compared with their closest nonendosymbiotic relatives. Both gammaproteobacterial genomes contain thousands of pseudogenes, consistent with a relatively recent shift from a free-living to an endosymbiotic lifestyle. Biosynthetic pathways of key metabolites are partitioned in complex interdependent patterns among the two gammaproteobacterial genomes, the Tremblaya genome, and horizontally acquired bacterial genes that are encoded on the mealybug nuclear genome. Although these two gammaproteobacterial endosymbionts have been acquired recently in evolutionary time, they have already evolved codependencies with each other, Tremblaya, and their insect host.
    MeSH term(s) Animals ; Betaproteobacteria/genetics ; Gammaproteobacteria/genetics ; Genome, Bacterial ; Hemiptera/genetics ; Hemiptera/microbiology ; Phylogeny ; Symbiosis/genetics
    Language English
    Publishing date 2021-07-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2495328-3
    ISSN 1759-6653 ; 1759-6653
    ISSN (online) 1759-6653
    ISSN 1759-6653
    DOI 10.1093/gbe/evab123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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