The Experts below are selected from a list of 1500 Experts worldwide ranked by ideXlab platform

Owen R. Davies - One of the best experts on this subject based on the ideXlab platform.

  • A molecular mechanism for LINC Complex branching by structurally diverse SUN-KASH 6:6 assemblies.
    eLife, 2021
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The Linker of Nucleoskeleton and Cytoskeleton (LINC) Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing, and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC Complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two constituent 3:3 Complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

  • a molecular mechanism for LINC Complex branching by structurally diverse sun kash 6 6 assemblies
    bioRxiv, 2020
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The LINC Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC Complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 Complex is incompatible with the current model of a linear LINC Complex and instead suggests the formation of a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

  • LINC Complex branching through structurally diverse SUN-KASH 6:6 assemblies
    2020
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The LINC Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC Complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 Complex is incompatible with the current model of a linear LINC Complex and instead suggests the formation of a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

Sue L. Jaspersen - One of the best experts on this subject based on the ideXlab platform.

  • SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion.
    Frontiers in cell and developmental biology, 2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into the chromatin by the SWR1 Complex, affecting multiple aspects of meiosis. We describe here a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the linker of nucleoskeleton, and cytoskeleton (LINC) Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton, promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during the meiotic prophase is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

  • SWR1-independent association of H2A.Z to the LINC Complex promotes meiotic chromosome motion
    2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into chromatin by the SWR1 Complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1δ mutant lacking H2A.Z, but it is unaffected in swr1δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

  • Yeast centrosome components form a noncanonical LINC Complex at the nuclear envelope insertion site
    The Journal of cell biology, 2019
    Co-Authors: Jingjing Chen, Jennifer M. Gardner, Sarah E. Smith, Sean A Mckinney, Brian D. Slaughter, Jay R. Unruh, Sue L. Jaspersen
    Abstract:

    Bipolar spindle formation in yeast requires insertion of centrosomes (known as spindle pole bodies [SPBs]) into fenestrated regions of the nuclear envelope (NE). Using structured illumination microscopy and bimolecular fluorescence complementation, we map protein distribution at SPB fenestrae and interrogate protein–protein interactions with high spatial resolution. We find that the Sad1-UNC-84 (SUN) protein Mps3 forms a ring-like structure around the SPB, similar to toroids seen for components of the SPB insertion network (SPIN). Mps3 and the SPIN component Mps2 (a Klarsicht-ANC-1-Syne-1 domain [KASH]–like protein) form a novel noncanonical linker of nucleoskeleton and cytoskeleton (LINC) Complex that is connected in both luminal and extraluminal domains at the site of SPB insertion. The LINC Complex also controls the distribution of a soluble SPIN component Bbp1. Taken together, our work shows that Mps3 is a fifth SPIN component and suggests both direct and indirect roles for the LINC Complex in NE remodeling.

  • Membrane insertion function for SUN-KASH Complex revealed by high resolution analysis of yeast centrosomes
    2018
    Co-Authors: Jingjing Chen, Jennifer M. Gardner, Sarah E. Smith, Sean A Mckinney, Brian D. Slaughter, Jay R. Unruh, Sue L. Jaspersen
    Abstract:

    Bipolar spindle formation in yeast requires insertion of centrosomes (known as spindle pole bodies (SPBs)) into fenestrated regions of the nuclear envelope (NE). Using structured-illumination microscopy and bimolecular fluorescence complementation, we map protein distribution at SPB fenestra and interrogate protein-protein interactions with high spatial resolution. We find that the Sad1-UNC-84 (SUN) protein Mps3 forms a ring-like structure around the SPB, similar to toroids seen for components of the SPB insertion network (SPIN). Mps3 and the SPIN component Mps2 (a Klarsicht-ANC-1-Syne-1 domain (KASH)-like protein) form a novel non-canonical linker of nucleoskeleton and cytoskeleton (LINC) Complex that is connected in both luminal and extraluminal domains. This hairpin-like LINC Complex forms during SPB insertion, suggesting it functions in NE reorganization at the pore membrane. The LINC Complex also controls the distribution of a soluble SPIN component Bbp1. Taken together our work shows that Mps3 is a fifth SPIN component and suggests both direct and indirect roles for the LINC Complex in NE remodeling.

Manickam Gurusaran - One of the best experts on this subject based on the ideXlab platform.

  • A molecular mechanism for LINC Complex branching by structurally diverse SUN-KASH 6:6 assemblies.
    eLife, 2021
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The Linker of Nucleoskeleton and Cytoskeleton (LINC) Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing, and meiotic chromosome movements. The canonical model is that 3:3 interactions between SUN and KASH proteins underlie the nucleocytoskeletal linkages provided by the LINC Complex. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two constituent 3:3 Complexes interact head-to-head. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 interface provides a molecular mechanism for the establishment of integrative and distributive connections between 3:3 structures within a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

  • a molecular mechanism for LINC Complex branching by structurally diverse sun kash 6 6 assemblies
    bioRxiv, 2020
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The LINC Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC Complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 Complex is incompatible with the current model of a linear LINC Complex and instead suggests the formation of a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

  • LINC Complex branching through structurally diverse SUN-KASH 6:6 assemblies
    2020
    Co-Authors: Manickam Gurusaran, Owen R. Davies
    Abstract:

    The LINC Complex mechanically couples cytoskeletal and nuclear components across the nuclear envelope to fulfil a myriad of cellular functions, including nuclear shape and positioning, hearing and meiotic chromosome movements. The canonical model of the LINC Complex is of individual linear nucleocytoskeletal linkages provided by 3:3 interactions between SUN and KASH proteins. Here, we provide crystallographic and biophysical evidence that SUN-KASH is a constitutive 6:6 Complex in which two SUN trimers interact back-to-back. A common SUN-KASH topology is achieved through structurally diverse 6:6 interaction mechanisms by distinct KASH proteins, including zinc-coordination by Nesprin-4. The SUN-KASH 6:6 Complex is incompatible with the current model of a linear LINC Complex and instead suggests the formation of a branched LINC Complex network. In this model, SUN-KASH 6:6 Complexes act as nodes for force distribution and integration between adjacent SUN and KASH molecules, enabling the coordinated transduction of large forces across the nuclear envelope.

Jennifer M. Gardner - One of the best experts on this subject based on the ideXlab platform.

  • SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion.
    Frontiers in cell and developmental biology, 2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into the chromatin by the SWR1 Complex, affecting multiple aspects of meiosis. We describe here a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the linker of nucleoskeleton, and cytoskeleton (LINC) Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton, promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during the meiotic prophase is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

  • SWR1-independent association of H2A.Z to the LINC Complex promotes meiotic chromosome motion
    2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into chromatin by the SWR1 Complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1δ mutant lacking H2A.Z, but it is unaffected in swr1δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

  • Yeast centrosome components form a noncanonical LINC Complex at the nuclear envelope insertion site
    The Journal of cell biology, 2019
    Co-Authors: Jingjing Chen, Jennifer M. Gardner, Sarah E. Smith, Sean A Mckinney, Brian D. Slaughter, Jay R. Unruh, Sue L. Jaspersen
    Abstract:

    Bipolar spindle formation in yeast requires insertion of centrosomes (known as spindle pole bodies [SPBs]) into fenestrated regions of the nuclear envelope (NE). Using structured illumination microscopy and bimolecular fluorescence complementation, we map protein distribution at SPB fenestrae and interrogate protein–protein interactions with high spatial resolution. We find that the Sad1-UNC-84 (SUN) protein Mps3 forms a ring-like structure around the SPB, similar to toroids seen for components of the SPB insertion network (SPIN). Mps3 and the SPIN component Mps2 (a Klarsicht-ANC-1-Syne-1 domain [KASH]–like protein) form a novel noncanonical linker of nucleoskeleton and cytoskeleton (LINC) Complex that is connected in both luminal and extraluminal domains at the site of SPB insertion. The LINC Complex also controls the distribution of a soluble SPIN component Bbp1. Taken together, our work shows that Mps3 is a fifth SPIN component and suggests both direct and indirect roles for the LINC Complex in NE remodeling.

  • Membrane insertion function for SUN-KASH Complex revealed by high resolution analysis of yeast centrosomes
    2018
    Co-Authors: Jingjing Chen, Jennifer M. Gardner, Sarah E. Smith, Sean A Mckinney, Brian D. Slaughter, Jay R. Unruh, Sue L. Jaspersen
    Abstract:

    Bipolar spindle formation in yeast requires insertion of centrosomes (known as spindle pole bodies (SPBs)) into fenestrated regions of the nuclear envelope (NE). Using structured-illumination microscopy and bimolecular fluorescence complementation, we map protein distribution at SPB fenestra and interrogate protein-protein interactions with high spatial resolution. We find that the Sad1-UNC-84 (SUN) protein Mps3 forms a ring-like structure around the SPB, similar to toroids seen for components of the SPB insertion network (SPIN). Mps3 and the SPIN component Mps2 (a Klarsicht-ANC-1-Syne-1 domain (KASH)-like protein) form a novel non-canonical linker of nucleoskeleton and cytoskeleton (LINC) Complex that is connected in both luminal and extraluminal domains. This hairpin-like LINC Complex forms during SPB insertion, suggesting it functions in NE reorganization at the pore membrane. The LINC Complex also controls the distribution of a soluble SPIN component Bbp1. Taken together our work shows that Mps3 is a fifth SPIN component and suggests both direct and indirect roles for the LINC Complex in NE remodeling.

Pedro A. San-segundo - One of the best experts on this subject based on the ideXlab platform.

  • SWR1-Independent Association of H2A.Z to the LINC Complex Promotes Meiotic Chromosome Motion.
    Frontiers in cell and developmental biology, 2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into the chromatin by the SWR1 Complex, affecting multiple aspects of meiosis. We describe here a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the linker of nucleoskeleton, and cytoskeleton (LINC) Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton, promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during the meiotic prophase is reduced in the htz1Δ mutant lacking H2A.Z, but it is unaffected in swr1Δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.

  • SWR1-independent association of H2A.Z to the LINC Complex promotes meiotic chromosome motion
    2020
    Co-Authors: Sara González-arranz, Jennifer M. Gardner, Sue L. Jaspersen, Neem J. Patel, Jonna Heldrich, Beatriz Santos, Jesús A. Carballo, Andreas Hochwagen, Pedro A. San-segundo
    Abstract:

    The H2A.Z histone variant is deposited into chromatin by the SWR1 Complex affecting multiple aspects of meiosis. Here we describe a SWR1-independent localization of H2A.Z at meiotic telomeres and the centrosome. We demonstrate that H2A.Z colocalizes and interacts with Mps3, the SUN component of the LINC Complex that spans the nuclear envelope and links meiotic telomeres to the cytoskeleton promoting meiotic chromosome movement. H2A.Z also interacts with the meiosis-specific Ndj1 protein that anchors telomeres to the nuclear periphery via Mps3. Telomeric localization of H2A.Z depends on Ndj1 and the N-terminal domain of Mps3. Although telomeric attachment to the nuclear envelope is maintained in the absence of H2A.Z, the distribution of Mps3 is altered. The velocity of chromosome movement during meiotic prophase I is reduced in the htz1δ mutant lacking H2A.Z, but it is unaffected in swr1δ cells. We reveal that H2A.Z is an additional LINC-associated factor that contributes to promote telomere-driven chromosome motion critical for error-free gametogenesis.