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LINC complex

Zeinab Jahed, Darya Fadavi, Uyen T Vu, Ehsaneddin Asgari, G W Gant Luxton, Mohammad R K Mofrad
The LINC complex is found in a wide variety of organisms and is formed by the transluminal interaction between outer- and inner-nuclear-membrane KASH and SUN proteins, respectively. Most extensively studied are SUN1 and SUN2 proteins, which are widely expressed in mammals. Although SUN1 and SUN2 play functionally redundant roles in several cellular processes, more recent studies have revealed diverse and distinct functions for SUN1. While several recent in vitro structural studies have revealed the molecular details of various fragments of SUN2, no such structural information is available for SUN1...
March 13, 2018: Biophysical Journal
You Kure Wu, Hiroki Umeshima, Junko Kurisu, Mineko Kengaku
Nuclear migration of newly born neurons is essential for cortex formation in the brain. The nucleus is translocated by actin and microtubules, yet the actual force generated by the interplay of these cytoskeletons remains elusive. High-resolution time-lapse observation of migrating murine cerebellar granule cells revealed that the nucleus actively rotates along the direction of its translocation, independently of centrosome motion. Pharmacological and molecular perturbation indicated that spin torque is primarily generated by microtubule motors through the LINC complex in the absence of actomyosin contractility...
March 8, 2018: Development
Jared Hennen, Cosmo A Saunders, Joachim D Mueller, G W Gant Luxton
Linker of nucleoskeleton and cytoskeleton (LINC) complexes are conserved molecular bridges within the nuclear envelope that mediate mechanical force transmission into the nucleoplasm. The core of the LINC complex is formed by a transluminal interaction between the outer and inner nuclear membrane KASH and SUN proteins, respectively. Mammals encode six KASH proteins and five SUN proteins. Recently, KASH proteins were shown to bind to the domain interfaces of trimeric SUN2 proteins in vitro However neither the existence of SUN2 trimers in living cells nor the extent to which other SUN proteins conform to this assembly state have been tested experimentally...
March 7, 2018: Molecular Biology of the Cell
Can Zhou, Li Rao, Catherine M Shanahan, Qiuping Zhang
Nesprins (nuclear envelope spectrin repeat proteins) are multi-isomeric scaffolding proteins. Nesprin-1 and -2 are highly expressed in skeletal and cardiac muscles and together with SUN (Sad1p/UNC84) domain-containing proteins form the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex at the nuclear envelope in association with lamin A/C and emerin. Mutations in nesprin-1/2 have been found in patients with autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD) as well as dilated cardiomyopathy (DCM)...
February 27, 2018: Biochemical Society Transactions
Hiromasa Imaizumi, Katsutoshi Sato, Asuka Nishihara, Kazumasa Minami, Masahiko Koizumi, Nariaki Matsuura, Miki Hieda
The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various process at the nuclear envelope including nuclear migration, mechanotransduction, chromatin tethering, and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1); a component of the LINC complex functions in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown...
February 21, 2018: Cancer Science
Brian Burke
Meiosis is a key processes of sexual reproduction in eukaryotes. By combining two cell division cycles with a single round of DNA replication meiosis provides a mechanism to generate haploid gametes. Coincidentally, processes involved in ensuring appropriate segregation of homologous chromosomes also result in genetic recombination and shuffling of genes between each generation. During the first meiotic prophase, rapid telomere-led chromosome movements facilitate alignment and pairing of homologous chromosomes...
January 29, 2018: Current Opinion in Cell Biology
Yang Xu, Wei Li, Huimin Ke, Wei Feng
LINC complexes span across the nuclear envelope and are assembled by SUN and KASH proteins. SUN1 and SUN2 are the two most abundant SUN proteins in mammals. In SUN2, the predicted coiled-coil domain preceding the SUN domain forms a three-helix bundle that constitutes an autoinhibitory domain (AID) to lock down the SUN domain. Here, we found that SUN1 also contains an AID preceding the SUN domain and solved the structure of the AID-SUN tandem of SUN1. SUN1 AID also adopts a three-helix bundle conformation that interacts with the SUN domain and keeps it in an autoinhibited state...
February 3, 2018: Biochemical and Biophysical Research Communications
Sylvain Fauquenoy, Valerie Migeot, Olivier Finet, Carlo Yague-Sanz, Olga Khorosjutina, Karl Ekwall, Damien Hermand
The cell fate decision leading to gametogenesis requires the convergence of multiple signals on the promoter of a master regulator. In fission yeast, starvation-induced signaling leads to the transcriptional induction of the ste11 gene, which encodes the central inducer of mating and gametogenesis, known as sporulation. We find that the long intergenic non-coding (linc) RNA rse1 is transcribed divergently upstream of the ste11 gene. During vegetative growth, rse1 directly recruits a Mug187-Lid2-Set1 complex that mediates cis repression at the ste11 promoter through SET3C-dependent histone deacetylation...
January 18, 2018: Current Biology: CB
Yixia Zhao, Fengqi Cao, Xiaohua Yu, Chuyan Chen, Jiao Meng, Ran Zhong, Yong Zhang, Dahai Zhu
Myogenic differentiation of skeletal muscle stem cells, also known satellite cells, is tightly orchestrated by extrinsic and intrinsic regulators. Basic fibroblast growth factor (FGF2) is well documented to be implicated in satellite cell self-renewal and differentiation by repressing MyoD. We recently identified a MyoD-regulated and skeletal muscle-specifically expressed long non-coding RNA Linc-RAM which enhances myogenic differentiation by facilitating MyoD/Baf60c/Brg1 complex assembly. Herein, we investigated the transcriptional regulation and intracellular signaling pathway in mediating Linc-RAM gene expression during muscle cell differentiation...
January 24, 2018: RNA Biology
Laura B Ferguson, Angela R Ozburn, Igor Ponomarev, Pamela Metten, Matthew Reilly, John C Crabbe, R Adron Harris, R Dayne Mayfield
Transcriptome-based drug discovery has identified new treatments for some complex diseases, but has not been applied to alcohol use disorder (AUD) or other psychiatric diseases, where there is a critical need for improved pharmacotherapies. High Drinking in the Dark (HDID-1) mice are a genetic model of AUD risk that have been selectively bred (from the HS/Npt line) to achieve intoxicating blood alcohol levels (BALs) after binge-like drinking. We compared brain gene expression of HDID-1 and HS/Npt mice to determine a molecular signature for genetic risk for high intensity, binge-like drinking...
December 18, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ruijun Zhu, Chenshu Liu, Gregg G Gundersen
The positioning and movement of the nucleus has recently emerged as an important aspect of cell migration. Understanding of nuclear positioning and movement has reached an apogee in studies of fibroblast migration. Specific nuclear positioning and movements have been described in the polarization of fibroblast for cell migration and in active migration in 2D and 3D environments. Here, we review recent studies that have uncovered novel molecular mechanisms that contribute to these events in fibroblasts. Many of these involve a connection between the nucleus and the cytoskeleton through the LINC complex composed of outer nuclear membrane nesprins and inner nuclear membrane SUN proteins...
December 11, 2017: Seminars in Cell & Developmental Biology
Yin Loon Lee, Brian Burke
One of the characteristics of eukaryotic cells is their structural plasticity associated with the ability to carry out a broad range of complex functions, both autonomously and as components of tissues and organs. Major cellular rearrangements can be observed in various systems from meiosis in fission yeast, through dermal differentiation in nematodes, to muscle and neuronal development in vertebrates. Each of these processes involves oftentimes dramatic relocation of the nucleus within the cell. During the last decade it has become apparent that the nuclear periphery represents a nexus of cytoskeletal interactions that are involved not only in nuclear movement but also in the distribution and dissemination of mechanical forces throughout the cell...
November 27, 2017: Seminars in Cell & Developmental Biology
Sergio Covarrubias, Elektra K Robinson, Barbara Shapleigh, Apple Vollmers, Solomon Katzman, Nicole Hanley, Nicholas Fong, Michael T McManus, Susan Carpenter
The innate immune system protects against infections by initiating an inducible inflammatory response. NF-kappa B (NF-KB) is one of the critical transcription factors controlling this complex response, but some aspects of its regulation remain unclear. For example, although long noncoding RNAs (lncRNAs) have been shown to critically regulate gene expression, only a fraction of these have been functionally characterized, and the extent to which lncRNAs control NF-KB expression is unknown. Here, we describe the generation of a GFP-based NF-KB reporter system in immortalized murine bone marrow-derived macrophages (iBMDMs)...
October 19, 2017: Journal of Biological Chemistry
Matthew John Stroud, Xi Fang, Jianlin Zhang, Nuno Guimarães-Camboa, Jennifer Veevers, Nancy D Dalton, Yusu Gu, William H Bradford, Kirk L Peterson, Sylvia M Evans, Larry Gerace, Ju Chen
Aims: Luma is a recently discovered, evolutionarily conserved protein expressed in mammalian heart that is associated with the LInker of Nucleoskeleton and Cytoskeleton (LINC) complex. The LINC complex structurally integrates the nucleus and the cytoplasm, and plays a critical role in mechanotransduction across the nuclear envelope. Mutations in several LINC components in both humans and mice result in various cardiomyopathies, implying they play essential, non-redundant roles. A single amino acid substitution of serine 358 to leucine (S358L) in LUMA is the unequivocal cause of a distinct form of arrhythmogenic cardiomyopathy...
October 12, 2017: Cardiovascular Research
Lauren K Whiteside, Doyanne Darnell, Karlee Jackson, Jin Wang, Joan Russo, Dennis M Donovan, Douglas F Zatzick
Collaborative Care is a comprehensive longitudinal care management strategy. The purpose of this pilot effectiveness-implementation hybrid study was to determine the feasibility of a Collaborative Care intervention initiated from the Emergency Department and proceeding longitudinally for six months for injured patients with prescription drug misuse (PDM). Adult patients presenting to an urban ED with an injury were screened for eligibility from 2/2015-8/2015. Eligible participants with a positive screen for PDM were enrolled in the 'ED-LINC' intervention which included the following elements: 1) active care coordination and linkage, 2) medication safety and utilization of opioid guidelines 3) longitudinal care management and 4) utilization of Electronic Medical Record (EMR) innovations such as the statewide Emergency Department Information Exchange (EDIE) and statewide prescription monitoring program information for assessment and follow-up...
November 2017: Journal of Substance Abuse Treatment
Ruijun Zhu, Susumu Antoku, Gregg G Gundersen
Nuclear movement is critical for developmental events, cell polarity, and migration and is usually mediated by linker of nucleoskeleton and cytoskeleton (LINC) complexes connecting the nucleus to cytoskeletal elements. Compared to active nuclear movement, relatively little is known about homeostatic positioning of nuclei, including whether it is an active process. To explore homeostatic nuclear positioning, we developed a method to displace nuclei in adherent cells using centrifugal force. Nuclei displaced by centrifugation rapidly recentered by mechanisms that depended on cell context...
October 23, 2017: Current Biology: CB
Shaoliang Peng, Shunyun Yang, Xiaochen Bo, Fei Li
More studies have been conducted using gene expression similarity to identify functional connections among genes, diseases and drugs. Gene Set Enrichment Analysis (GSEA) is a powerful analytical method for interpreting gene expression data. However, due to its enormous computational overhead in the estimation of significance level step and multiple hypothesis testing step, the computation scalability and efficiency are poor on large-scale datasets. We proposed paraGSEA for efficient large-scale transcriptome data analysis...
September 29, 2017: Nucleic Acids Research
Alexandre Janin, Delphine Bauer, Francesca Ratti, Gilles Millat, Alexandre Méjat
Since the identification of the first disease causing mutation in the gene coding for emerin, a transmembrane protein of the inner nuclear membrane, hundreds of mutations and variants have been found in genes encoding for nuclear envelope components. These proteins can be part of the inner nuclear membrane (INM), such as emerin or SUN proteins, outer nuclear membrane (ONM), such as Nesprins, or the nuclear lamina, such as lamins A and C. However, they physically interact with each other to insure the nuclear envelope integrity and mediate the interactions of the nuclear envelope with both the genome, on the inner side, and the cytoskeleton, on the outer side...
August 30, 2017: Orphanet Journal of Rare Diseases
Ping Li, Maria Stumpf, Rolf Müller, Ludwig Eichinger, Gernot Glöckner, Angelika A Noegel
SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction...
August 22, 2017: Scientific Reports
Kateryna Fal, Atef Asnacios, Marie-Edith Chabouté, Olivier Hamant
In animals, it is now well established that forces applied at the cell surface are propagated through the cytoskeleton to the nucleus, leading to deformations of the nuclear structure and, potentially, to modification of gene expression. Consistently, altered nuclear mechanics has been related to many genetic disorders, such as muscular dystrophy, cardiomyopathy and progeria. In plants, the integration of mechanical signals in cell and developmental biology has also made great progress. Yet, while the link between cell wall stresses and cytoskeleton is consolidated, such cortical mechanical cues have not been integrated with the nucleoskeleton...
August 2017: Biophysical Reviews
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