The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform

Daniel A Starr - One of the best experts on this subject based on the ideXlab platform.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans independently from its KASH or actin binding Domains
    eLife, 2021
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Jessica Bolivar, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans without its KASH or actin binding Domains
    bioRxiv, 2020
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.

  • Role of KASH domain lengths in the regulation of LINC complexes
    Molecular biology of the cell, 2019
    Co-Authors: Zeinab Jahed, Hongyan Hao, Vyom Thakkar, Venecia A. Valdez, Akshay Rathish, Chris Tolentino, Samuel C. J. Kim, Darya Fadavi, Daniel A Starr
    Abstract:

    The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic Domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN-KASH complex. We show that longer KASH Domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH Domains. In agreement with our models, our in vivo results show that swapping the KASH Domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans.

  • KASH n karry the KASH domain family of cargo specific cytoskeletal adaptor proteins
    BioEssays, 2005
    Co-Authors: Daniel A Starr, Janice A Fischer
    Abstract:

    A diverse family of proteins has been discovered with a small C-terminal KASH domain in common. KASH domain proteins are localized uniquely to the outer nuclear envelope, enabling their cytoplasmic extensions to tether the nucleus to actin filaments or microtubules. KASH Domains are targeted to the outer nuclear envelope by SUN Domains of inner nuclear envelope proteins. Several KASH protein genes were discovered as mutant alleles in model organisms with defects in developmentally regulated nuclear positioning. Recently, KASH-less isoforms have been found that connect the cytoskeleton to organelles other than the nucleus. A widened view of these proteins is now emerging, where KASH proteins and their KASH-less counterparts are cargo-specific adaptors that not only link organelles to the cytoskeleton but also regulate developmentally specific organelle movements.

Hongyan Hao - One of the best experts on this subject based on the ideXlab platform.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans independently from its KASH or actin binding Domains
    eLife, 2021
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Jessica Bolivar, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans without its KASH or actin binding Domains
    bioRxiv, 2020
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.

  • Role of KASH domain lengths in the regulation of LINC complexes
    Molecular biology of the cell, 2019
    Co-Authors: Zeinab Jahed, Hongyan Hao, Vyom Thakkar, Venecia A. Valdez, Akshay Rathish, Chris Tolentino, Samuel C. J. Kim, Darya Fadavi, Daniel A Starr
    Abstract:

    The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic Domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN-KASH complex. We show that longer KASH Domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH Domains. In agreement with our models, our in vivo results show that swapping the KASH Domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans.

Natalie E Cain - One of the best experts on this subject based on the ideXlab platform.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans independently from its KASH or actin binding Domains
    eLife, 2021
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Jessica Bolivar, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans without its KASH or actin binding Domains
    bioRxiv, 2020
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.

Leslie A Guerrero - One of the best experts on this subject based on the ideXlab platform.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans independently from its KASH or actin binding Domains
    eLife, 2021
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Jessica Bolivar, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans without its KASH or actin binding Domains
    bioRxiv, 2020
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.

Laura E Jameson - One of the best experts on this subject based on the ideXlab platform.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans independently from its KASH or actin binding Domains
    eLife, 2021
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Jessica Bolivar, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of linker of nucleoskeleton and cytoskeleton (LINC) complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the transmembrane (TM) span. In anc-1 mutants, the endoplasmic reticulum ER, mitochondria, and lipid droplets were unanchored, moving throughout the cytoplasm. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and other organelles in place.

  • the nesprin 1 2 ortholog anc 1 regulates organelle positioning in c elegans without its KASH or actin binding Domains
    bioRxiv, 2020
    Co-Authors: Hongyan Hao, Shilpi Kalra, Laura E Jameson, Leslie A Guerrero, Natalie E Cain, Daniel A Starr
    Abstract:

    KASH proteins in the outer nuclear membrane comprise the cytoplasmic half of LINC complexes that connect nuclei to the cytoskeleton. Caenorhabditis elegans ANC-1, an ortholog of Nesprin-1/2, contains actin-binding and KASH Domains at opposite ends of a long spectrin-like region. Deletion of either the KASH or calponin homology (CH) Domains does not completely disrupt nuclear positioning, suggesting neither KASH nor CH Domains are essential. Deletions in the spectrin-like region of ANC-1 led to significant defects, but only recapitulated the null phenotype in combination with mutations in the trans-membrane span. In anc-1 mutants, the ER was unanchored, moving throughout the cytoplasm, and often fragmented. The data presented here support a cytoplasmic integrity model where ANC-1 localizes to the ER membrane and extends into the cytoplasm to position nuclei, ER, mitochondria, and likely other organelles in place.