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  1. Article ; Online: Interface extension is a continuum property suggesting a linkage between AP contractile and DV lengthening processes.

    Vanderleest, Timothy E / Xie, Yi / Smits, Celia / Blankenship, J Todd / Loerke, Dinah

    Molecular biology of the cell

    2022  Volume 33, Issue 14, Page(s) ar142

    Abstract: ... In the ... ...

    Abstract In the early
    MeSH term(s) Animals ; Drosophila ; Drosophila Proteins ; Myosins ; Mechanical Phenomena ; Actins ; Body Patterning
    Chemical Substances Drosophila Proteins ; Myosins (EC 3.6.4.1) ; Actins
    Language English
    Publishing date 2022-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E21-07-0352
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2853: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MO 410: Show issues

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  2. Article ; Online: A PtdIns(3,4,5)P

    Miao, Hui / Vanderleest, Timothy E / Budhathoki, Rashmi / Loerke, Dinah / Blankenship, J Todd

    Developmental cell

    2021  Volume 56, Issue 18, Page(s) 2579–2591.e4

    Abstract: Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be ratcheting mechanisms that drive ... ...

    Abstract Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating contractile forces before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be ratcheting mechanisms that drive processive transformations in cell shape. Previous work has shown that force generation is coordinated with endocytic remodeling; however, how ratcheting becomes engaged at specific cell surfaces remains unclear. Here, we report that PtdIns(3,4,5)P
    MeSH term(s) Actin Cytoskeleton/metabolism ; Actomyosin/metabolism ; Animals ; Cell Membrane/metabolism ; Cell Polarity/physiology ; Cell Shape/physiology ; Cytoskeleton/metabolism ; Drosophila ; Drosophila Proteins/metabolism ; Epithelial Cells/metabolism ; Epithelium/metabolism ; Morphogenesis/physiology ; Phosphatidylinositols/metabolism
    Chemical Substances Drosophila Proteins ; Phosphatidylinositols ; Actomyosin (9013-26-7)
    Language English
    Publishing date 2021-09-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2021.08.016
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    Zs.A 5742: Show issues Location:
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    Zs.MG 76: Show issues

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  3. Article ; Online: Cell ratcheting through the Sbf RabGEF directs force balancing and stepped apical constriction.

    Miao, Hui / Vanderleest, Timothy E / Jewett, Cayla E / Loerke, Dinah / Blankenship, J Todd

    The Journal of cell biology

    2019  Volume 218, Issue 11, Page(s) 3845–3860

    Abstract: ... ...

    Abstract During
    MeSH term(s) Animals ; Cell Membrane/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; rab GTP-Binding Proteins/metabolism
    Chemical Substances Drosophila Proteins ; Sbf protein, Drosophila ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2019-09-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.201905082
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  4. Article: APOE3

    Perez-Corredor, Paula / Vanderleest, Timothy E / Vacano, Guido N / Sanchez, Justin S / Villalba-Moreno, Nelson D / Marino, Claudia / Krasemann, Susanne / Mendivil-Perez, Miguel A / Aguillón, David / Jiménez-Del-Río, Marlene / Baena, Ana / Sepulveda-Falla, Diego / Lopera, Francisco / Quiroz, Yakeel T / Arboleda-Velasquez, Joseph F / Mazzarino, Randall C

    Frontiers in molecular neuroscience

    2024  Volume 17, Page(s) 1373568

    Abstract: A patient with ... ...

    Abstract A patient with the
    Language English
    Publishing date 2024-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2024.1373568
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  5. Article ; Online: Vertex sliding drives intercalation by radial coupling of adhesion and actomyosin networks during

    Vanderleest, Timothy E / Smits, Celia M / Xie, Yi / Jewett, Cayla E / Blankenship, J Todd / Loerke, Dinah

    eLife

    2018  Volume 7

    Abstract: Oriented cell intercalation is an essential developmental process that shapes tissue morphologies through the directional insertion of cells between their neighbors. Previous research has focused on properties of ... ...

    Abstract Oriented cell intercalation is an essential developmental process that shapes tissue morphologies through the directional insertion of cells between their neighbors. Previous research has focused on properties of cell
    MeSH term(s) Actomyosin/metabolism ; Animals ; Anisotropy ; Body Patterning ; Cadherins/metabolism ; Cell Adhesion ; Cell Polarity ; Drosophila melanogaster/cytology ; Drosophila melanogaster/embryology ; Embryo, Nonmammalian/cytology ; Morphogenesis ; Mutation/genetics ; Myosin Type II/metabolism
    Chemical Substances Cadherins ; Actomyosin (9013-26-7) ; Myosin Type II (EC 3.6.1.-)
    Language English
    Publishing date 2018-07-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.34586
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  6. Article ; Online: APOE Christchurch-mimetic therapeutic antibody reduces APOE-mediated toxicity and tau phosphorylation.

    Marino, Claudia / Perez-Corredor, Paula / O'Hare, Michael / Heuer, Annie / Chmielewska, Natalia / Gordon, Harper / Chandrahas, Anita S / Gonzalez-Buendia, Lucia / Delgado-Tirado, Santiago / Doan, Tri H / Vanderleest, Timothy E / Arevalo-Alquichire, Said / Obar, Robert A / Ortiz-Cordero, Carolina / Villegas, Andres / Sepulveda-Falla, Diego / Kim, Leo A / Lopera, Francisco / Mahley, Robert /
    Huang, Yadong / Quiroz, Yakeel T / Arboleda-Velasquez, Joseph F

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2023  Volume 20, Issue 2, Page(s) 819–836

    Abstract: Introduction: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).: ... ...

    Abstract Introduction: We discovered that the APOE3 Christchurch (APOE3Ch) variant may provide resistance to Alzheimer's disease (AD). This resistance may be due to reduced pathological interactions between ApoE3Ch and heparan sulfate proteoglycans (HSPGs).
    Methods: We developed and characterized the binding, structure, and preclinical efficacy of novel antibodies targeting human ApoE-HSPG interactions.
    Results: We found that one of these antibodies, called 7C11, preferentially bound ApoE4, a major risk factor for sporadic AD, and disrupts heparin-ApoE4 interactions. We also determined the crystal structure of a Fab fragment of 7C11 and used computer modeling to predict how it would bind to ApoE. When we tested 7C11 in mouse models, we found that it reduced recombinant ApoE-induced tau pathology in the retina of MAPT*P301S mice and curbed pTau S396 phosphorylation in brains of systemically treated APOE4 knock-in mice. Targeting ApoE-HSPG interactions using 7C11 antibody may be a promising approach to developing new therapies for AD.
    MeSH term(s) Mice ; Humans ; Animals ; Apolipoprotein E4/genetics ; Apolipoprotein E4/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Phosphorylation ; Apolipoproteins E/metabolism ; Alzheimer Disease/pathology ; Immunologic Factors ; Apolipoprotein E3/genetics ; Apolipoprotein E3/metabolism
    Chemical Substances Apolipoprotein E4 ; Heparan Sulfate Proteoglycans ; Apolipoproteins E ; Immunologic Factors ; Apolipoprotein E3
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13436
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    Zs.A 6316: Show issues Location:
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    Zs.MO 540: Show issues

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  7. Article ; Online: Planar polarized Rab35 functions as an oscillatory ratchet during cell intercalation in the Drosophila epithelium.

    Jewett, Cayla E / Vanderleest, Timothy E / Miao, Hui / Xie, Yi / Madhu, Roopa / Loerke, Dinah / Blankenship, J Todd

    Nature communications

    2017  Volume 8, Issue 1, Page(s) 476

    Abstract: The coordination between membrane trafficking and actomyosin networks is essential to the regulation of cell and tissue shape. Here, we examine Rab protein distributions during Drosophila epithelial tissue remodeling and show that Rab35 is dynamically ... ...

    Abstract The coordination between membrane trafficking and actomyosin networks is essential to the regulation of cell and tissue shape. Here, we examine Rab protein distributions during Drosophila epithelial tissue remodeling and show that Rab35 is dynamically planar polarized. Rab35 compartments are enriched at contractile interfaces of intercalating cells and provide the first evidence of interfacial monopolarity. When Rab35 function is disrupted, apical area oscillations still occur and contractile steps are observed. However, contractions are followed by reversals and interfaces fail to shorten, demonstrating that Rab35 functions as a ratchet ensuring unidirectional movement. Although actomyosin forces have been thought to drive interface contraction, initiation of Rab35 compartments does not require Myosin II function. However, Rab35 compartments do not terminate and continue to grow into large elongated structures following actomyosin disruption. Finally, Rab35 represents a common contractile cell-shaping mechanism, as mesoderm invagination fails in Rab35 compromised embryos and Rab35 localizes to constricting surfaces.Various stages of tissue morphogenesis involve the contraction of epithelial surfaces. Here, the authors identify the Rab GTPase Rab35 as an essential component of this contractile process, which functions as a membrane ratchet to ensure unidirectional movement of intercalating cells.
    MeSH term(s) Actomyosin/metabolism ; Animals ; Animals, Genetically Modified ; Cell Compartmentation ; Cell Membrane/metabolism ; Cell Polarity ; Cell Shape ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/cytology ; Drosophila melanogaster/genetics ; Endosomes/metabolism ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Myosin Type II/metabolism ; rab GTP-Binding Proteins/genetics ; rab GTP-Binding Proteins/metabolism ; rab5 GTP-Binding Proteins/metabolism
    Chemical Substances Drosophila Proteins ; Actomyosin (9013-26-7) ; Myosin Type II (EC 3.6.1.-) ; Rab11 protein, Drosophila (EC 3.6.1.-) ; Rab35 protein, Drosophila (EC 3.6.1.-) ; Rab5 protein, Drosophila (EC 3.6.1.47.) ; rab GTP-Binding Proteins (EC 3.6.5.2) ; rab5 GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2017-09-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2041-1723
    ISSN (online) 2041-1723
    DOI 10.1038/s41467-017-00553-0
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  8. Article ; Online: Exocyst-Dependent Membrane Addition Is Required for Anaphase Cell Elongation and Cytokinesis in Drosophila.

    Giansanti, Maria Grazia / Vanderleest, Timothy E / Jewett, Cayla E / Sechi, Stefano / Frappaolo, Anna / Fabian, Lacramioara / Robinett, Carmen C / Brill, Julie A / Loerke, Dinah / Fuller, Margaret T / Blankenship, J Todd

    PLoS genetics

    2015  Volume 11, Issue 11, Page(s) e1005632

    Abstract: Mitotic and cytokinetic processes harness cell machinery to drive chromosomal segregation and the physical separation of dividing cells. Here, we investigate the functional requirements for exocyst complex function during cell division in vivo, and ... ...

    Abstract Mitotic and cytokinetic processes harness cell machinery to drive chromosomal segregation and the physical separation of dividing cells. Here, we investigate the functional requirements for exocyst complex function during cell division in vivo, and demonstrate a common mechanism that directs anaphase cell elongation and cleavage furrow progression during cell division. We show that onion rings (onr) and funnel cakes (fun) encode the Drosophila homologs of the Exo84 and Sec8 exocyst subunits, respectively. In onr and fun mutant cells, contractile ring proteins are recruited to the equatorial region of dividing spermatocytes. However, cytokinesis is disrupted early in furrow ingression, leading to cytokinesis failure. We use high temporal and spatial resolution confocal imaging with automated computational analysis to quantitatively compare wild-type versus onr and fun mutant cells. These results demonstrate that anaphase cell elongation is grossly disrupted in cells that are compromised in exocyst complex function. Additionally, we observe that the increase in cell surface area in wild type peaks a few minutes into cytokinesis, and that onr and fun mutant cells have a greatly reduced rate of surface area growth specifically during cell division. Analysis by transmission electron microscopy reveals a massive build-up of cytoplasmic astral membrane and loss of normal Golgi architecture in onr and fun spermatocytes, suggesting that exocyst complex is required for proper vesicular trafficking through these compartments. Moreover, recruitment of the small GTPase Rab11 and the PITP Giotto to the cleavage site depends on wild-type function of the exocyst subunits Exo84 and Sec8. Finally, we show that the exocyst subunit Sec5 coimmunoprecipitates with Rab11. Our results are consistent with the exocyst complex mediating an essential, coordinated increase in cell surface area that potentiates anaphase cell elongation and cleavage furrow ingression.
    MeSH term(s) Anaphase ; Animals ; Cell Cycle ; Drosophila/cytology
    Language English
    Publishing date 2015-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1005632
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