Implications for Diverse Functions of the LINC Complexes Based on the Structure

Hieda, Miki

doi:10.3390/cells6010003

Cited by 31 publications

(26 citation statements)

References 85 publications

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“…Another case for higher-order organization of LINC complex involves how nuclei move rearward in wounded NIH3T3 fibroblasts. During nuclear migration, linear arrays of SUN2-Nesprin -2G LINC complexes, termed transmembrane actinassociated nuclear (TAN) lines, assemble to tether the nuclei to moving actin cables [9,31]. As a more extreme example, LINC complex proteins involved in meiotic chromosome dynamics and telomere bouquet formation redistribute and concentrate in large patches associated with chromosome ends [6,[46][47][48].…”

Section: Other Factors That Influence Force Transmission Through Lincmentioning

confidence: 99%

“…It has also been proposed that a cysteine adjacent to the SUN domain of SUN1 protein is able to form intermolecular disulfide bonds with neighboring SUN trimers [44,50]. The specific requirement of mammalian SUN1, but not SUN2, during meiotic chromosome pairing, might be associated with the ability of SUN1 to more easily form higher-order structures than SUN2 [9,43,44,49]. Interestingly, a recent study has shown different mechanisms involved in homeostatic nuclear positioning under centrifugal force.…”

Section: Other Factors That Influence Force Transmission Through Lincmentioning

confidence: 99%

“…LINC complexes are made of SUN (Sad1, UNC-84) proteins in the inner nuclear membrane and KASH (Klarsicht, ANC-1, and Syne Homology) proteins in the outer nuclear membrane [7]. The central interaction occurs in the lumen of the nuclear envelope near the outer nuclear membrane, between a trimer of conserved SUN domains about 175 residues each and C-terminal KASH peptides of 10 to 32 residues ( Figure 1) [8][9][10][11][12]. SUN proteins then extend across the perinuclear space, cross the inner nuclear membrane and interact with lamins or other proteins in the nucleus, including chromatin and telomeric proteins [6,13,14].…”

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confidence: 99%

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SUN/KASH interactions facilitate force transmission across the nuclear envelope

Hao

Starr

2019

Nucleus

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LINC complexes (Linker of Nucleoskeleton and Cytoskeleton), consisting of inner nuclear membrane SUN (Sad1, UNC-84) proteins and outer nuclear membrane KASH (Klarsicht, ANC-1, and Syne Homology) proteins, are essential for nuclear positioning, cell migration and chromosome dynamics. To test the in vivo functions of conserved interfaces revealed by crystal structures, Cain et al used a combination of Caenorhabditis elegans genetics, imaging in cultured NIH 3T3 fibroblasts, and Molecular Dynamic simulations, to study SUN-KASH interactions. Conserved aromatic residues at the -7 position of the C-termini of KASH proteins and conserved disulfide bonds in LINC complexes play important roles in force transmission across the nuclear envelope. Other properties of LINC complexes, such as the helices preceding the SUN domain, the longer coiled-coils spanning the perinuclear space and higher-order organization may also function to transmit mechanical forces generated by the cytoskeleton across the nuclear envelope.

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Section: Other Factors That Influence Force Transmission Through Lincmentioning

confidence: 99%

Section: Other Factors That Influence Force Transmission Through Lincmentioning

confidence: 99%

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confidence: 99%

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SUN/KASH interactions facilitate force transmission across the nuclear envelope

Hao

Starr

2019

Nucleus

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“…The LINC complex was discovered relatively recently, but has been shown to be highly conserved in eukaryotes, with myriad functions as described in numerous reviews [4][5][6][7][8][9]. These LINC-mediated functions include regulation of nuclear shape and position [10,11], mechanosensory signal transduction [12], control of cell division, intranuclear architecture and gene regulation [13][14][15], and the specialized behavior of meiotic chromosomes to ensure segregation and fertility [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

MLKS2 is an ARM domain and F-actin-associated KASH protein that functions in stomatal complex development and meiotic chromosome segregation

Gumber

McKenna

Tolmie

et al. 2019

Nucleus

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The linker of nucleoskeleton and cytoskeleton (LINC) complex is an essential multi-protein structure spanning the eukaryotic nuclear envelope. The LINC complex functions to maintain nuclear architecture, positioning, and mobility, along with specialized functions in meiotic prophase and chromosome segregation. Members of the LINC complex were recently identified in maize, an important scientific and agricultural grass species. Here we characterized Maize LINC KASH AtSINE-like2, MLKS2 , which encodes a highly conserved SINE-group plant KASH protein with characteristic N-terminal armadillo repeats (ARM). Using a heterologous expression system, we showed that actively expressed GFP-MLKS2 is targeted to the nuclear periphery and colocalizes with F-actin and the endoplasmic reticulum, but not microtubules in the cell cortex. Expression of GFP-MLKS2, but not GFP-MLKS2ΔARM, resulted in nuclear anchoring. Genetic analysis of transposon-insertion mutations, mlks2-1 and mlks2-2 , showed that the mutant phenotypes were pleiotropic, affecting root hair nuclear morphology, stomatal complex development, multiple aspects of meiosis, and pollen viability. In male meiosis, the mutants showed defects for bouquet-stage telomere clustering, nuclear repositioning, perinuclear actin accumulation, dispersal of late prophase bivalents, and meiotic chromosome segregation. These findings support a model in which the nucleus is connected to cytoskeletal F-actin through the ARM-domain, predicted alpha solenoid structure of MLKS2. Functional conservation of MLKS2 was demonstrated through genetic rescue of the misshapen nuclear phenotype of an Arabidopsis (triple- WIP ) KASH mutant. This study establishes a role for the SINE-type KASH proteins in affecting the dynamic nuclear phenomena required for normal plant growth and fertility. Abbreviations : FRAP: Fluorescence recovery after photobleaching; DPI: Days post infiltration; OD: Optical density; MLKS2: Maize LINC KASH AtSINE-like2; LINC: Linker of nucleoskeleton and cytoskeleton; NE: Nuclear envelope; INM: Inner nuclear membrane; ONM: Outer nuclear membrane

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“…For chromosome motion during meiotic prophase I, the LINC complex transmits cytoskeleton‐driven forces to the telomeres and thus to chromosomes. The LINC complex also plays a role in nuclear positioning and migration in somatic cells (Hieda, ).…”

Section: Introductionmentioning

confidence: 99%

Meiosis‐specific cohesin component, Rec8, promotes the localization of Mps3 SUN domain protein on the nuclear envelope

et al. 2018

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Proteins in the nuclear envelope (NE) play a role in the dynamics and functions of the nucleus and of chromosomes during mitosis and meiosis. Mps3, a yeast NE protein with a conserved SUN domain, predominantly localizes on a yeast centrosome equivalent, spindle pole body (SPB), in mitotic cells. During meiosis, Mps3, together with SPB, forms a distinct multiple ensemble on NE. How meiosis-specific NE localization of Mps3 is regulated remains largely unknown. In this study, we found that a meiosis-specific component of the protein complex essential for sister chromatid cohesion, Rec8, binds to Mps3 during meiosis and controls Mps3 localization and proper dynamics on NE. Ectopic expression of Rec8 in mitotic yeast cells induced the formation of Mps3 patches/foci on NE. This required the cohesin regulator, WAPL ortholog, Rad61/Wpl1, suggesting that a meiosis-specific cohesin complex with Rec8 controls NE localization of Mps3. We also observed that two domains of the nucleoplasmic region of Mps3 are essential for NE localization of Mps3 in mitotic as well as meiotic cells. We speculate that the interaction of Mps3 with the meiosis-specific cohesin in the nucleoplasm is a key determinant for NE localization/ function of Mps3.

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Implications for Diverse Functions of the LINC Complexes Based on the Structure

Cited by 31 publications

References 85 publications

SUN/KASH interactions facilitate force transmission across the nuclear envelope

SUN/KASH interactions facilitate force transmission across the nuclear envelope

MLKS2 is an ARM domain and F-actin-associated KASH protein that functions in stomatal complex development and meiotic chromosome segregation

Meiosis‐specific cohesin component, Rec8, promotes the localization of Mps3 SUN domain protein on the nuclear envelope

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