Lamins at the Crossroads of Mechanosignaling
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Role of Nuclear Lamin B1 in Cell Proliferation and Senescence
Downloaded from genesdev.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press The role of nuclear lamin B1 in cell proliferation and senescence Takeshi Shimi,1 Veronika Butin-Israeli,1 Stephen A. Adam,1 Robert B. Hamanaka,2 Anne E. Goldman,1 Catherine A. Lucas,1 Dale K. Shumaker,1 Steven T. Kosak,1 Navdeep S. Chandel,2 and Robert D. Goldman1,3 1Department of Cell and Molecular Biology, 2Department of Medicine, Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA Nuclear lamin B1 (LB1) is a major structural component of the nucleus that appears to be involved in the regulation of many nuclear functions. The results of this study demonstrate that LB1 expression in WI-38 cells decreases during cellular senescence. Premature senescence induced by oncogenic Ras also decreases LB1 expression through a retinoblastoma protein (pRb)-dependent mechanism. Silencing the expression of LB1 slows cell proliferation and induces premature senescence in WI-38 cells. The effects of LB1 silencing on proliferation require the activation of p53, but not pRb. However, the induction of premature senescence requires both p53 and pRb. The proliferation defects induced by silencing LB1 are accompanied by a p53-dependent reduction in mitochondrial reactive oxygen species (ROS), which can be rescued by growth under hypoxic conditions. In contrast to the effects of LB1 silencing, overexpression of LB1 increases the proliferation rate and delays the onset of senescence of WI-38 cells. This overexpression eventually leads to cell cycle arrest at the G1/S boundary. -
Differential Expression of Two Neuronal Intermediate-Filament Proteins, Peripherin and the Low-Molecular-Mass Neurofilament Prot
The Journal of Neuroscience, March 1990, fO(3): 764-764 Differential Expression of Two Neuronal Intermediate-Filament Proteins, Peripherin and the Low-Molecular-Mass Neurofilament Protein (NF-L), During the Development of the Rat Michel Escurat,’ Karima Djabali,’ Madeleine Gumpel,2 Franqois Gras,’ and Marie-Madeleine Portier’ lCollBne de France, Biochimie Cellulaire, 75231 Paris Cedex 05, France, *HBpital de la Salpktricke, Unite INSERM 134, 75651Paris Cedex 13, France The expression of peripherin, an intermediate filament pro- and Freeman, 1978), now more generally referred to respectively tein, had been shown by biochemical methods to be local- as high-, middle-, and low-molecular-mass NFP (NF-H, NF-M, ized in the neurons of the PNS. Using immunohistochemical and NF-L). These proteins are expressed in most mature neu- methods, we analyzed this expression more extensively dur- ronal populations belonging either to the CNS or to the PNS; ing the development of the rat and compared it with that of developing neurons generally do not express any of them until the low-molecular-mass neurofilament protein (NF-L), which they become postmitotic (Tapscott et al., 198 la). is expressed in every neuron of the CNS and PNS. We, however, described another IFP with a molecular weight The immunoreactivity of NF-L is first apparent at the 25 of about 57 kDa, which we had first observed in mouse neu- somite stage (about 11 d) in the ventral horn of the spinal roblastoma cell lines and which was also expressed in rat pheo- medulla and in the posterior part of the rhombencephalon. chromocytoma PC1 2 cell line. -
Supplementary Materials
1 Supplementary Materials: Supplemental Figure 1. Gene expression profiles of kidneys in the Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice. (A) A heat map of microarray data show the genes that significantly changed up to 2 fold compared between Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice (N=4 mice per group; p<0.05). Data show in log2 (sample/wild-type). 2 Supplemental Figure 2. Sting signaling is essential for immuno-phenotypes of the Fcgr2b-/-lupus mice. (A-C) Flow cytometry analysis of splenocytes isolated from wild-type, Fcgr2b-/- and Fcgr2b-/-. Stinggt/gt mice at the age of 6-7 months (N= 13-14 per group). Data shown in the percentage of (A) CD4+ ICOS+ cells, (B) B220+ I-Ab+ cells and (C) CD138+ cells. Data show as mean ± SEM (*p < 0.05, **p<0.01 and ***p<0.001). 3 Supplemental Figure 3. Phenotypes of Sting activated dendritic cells. (A) Representative of western blot analysis from immunoprecipitation with Sting of Fcgr2b-/- mice (N= 4). The band was shown in STING protein of activated BMDC with DMXAA at 0, 3 and 6 hr. and phosphorylation of STING at Ser357. (B) Mass spectra of phosphorylation of STING at Ser357 of activated BMDC from Fcgr2b-/- mice after stimulated with DMXAA for 3 hour and followed by immunoprecipitation with STING. (C) Sting-activated BMDC were co-cultured with LYN inhibitor PP2 and analyzed by flow cytometry, which showed the mean fluorescence intensity (MFI) of IAb expressing DC (N = 3 mice per group). 4 Supplemental Table 1. Lists of up and down of regulated proteins Accession No. -
Vitellogenic Oocytes
CELL STRUCTURE AND FUNCTION 26: 693–703 (2001) © 2001 by Japan Society for Cell Biology Somatic Lamins in Germinal Vesicles of Goldfish (Carassius auratus) Vitellogenic Oocytes Akihiko Yamaguchi1 and Yoshitaka Nagahama Laboratory of Reproductive Biology, Department of Developmental Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan 1Present address: Laboratory of Marine Biology, Department of Animal and Marine Bioresouruce Science, Faculty of Agriculture, Kyushu Univsity, Fukuoka, Japan ABSTRACT. In fish and amphibians, B-type lamins are divided into somatic (B1, B2) and oocyte-type (B3) lamins. In this study, we purified nuclear lamins from rainbow trout erythrocytes, raised an anti-lamin mono- clonal antibody (L-200) that recognizes goldfish somatic-lamins, and isolated cDNAs encoding goldfish B-type lamins (B1 and B2) from a goldfish cell culture cDNA library. Goldfish B-type lamins are structurally similar to lamins found in other vertebrates with minor amino acid substitutions in the conserved region. Western blot anal- ysis showed that goldfish oocytes contained mainly GV-lamin B3 as well as some somatic lamins. Laser-confocal microscope observations revealed that lamin B3 was present only in GV nuclear lamina, whereas somatic lamins were present in dense fibrillar structures throughout nuclear gels of isolated GVs. Similar nuclear filamentous structures were also observed in GVs of paraffin embedded oocytes. Epitope mapping indicated that L-200 recognized a conserved region containing a short stretch of the -helix coiled-coil rod domain (Y(E/Q)(Q/E)LL). A similar motif is also present in other cytoplasmic intermediate filaments (i.e., vimentin, desmin, peripherin and GFAP). Taken together, these findings suggest that lamins or lamin-related intermediate filaments are an impor- tant component of the interior architecture of goldfish vitellogenic oocyte nuclei (GVs). -
Tubulin: Are They Linced?
cells Review Microtubular and Nuclear Functions of γ-Tubulin: Are They LINCed? Jana Chumová, Hana Kourová, Lucie Trögelová, Petr Halada and Pavla Binarová * Institute of Microbiology of the Czech Academy of Sciences, Vídeˇnská 1083, 142 20 Prague, Czech Republic; [email protected] (J.C.); [email protected] (H.K.); [email protected] (L.T.); [email protected] (P.H.) * Correspondence: [email protected]; Tel.: +420-241-062-130 Received: 8 February 2019; Accepted: 14 March 2019; Published: 19 March 2019 Abstract: γ-Tubulin is a conserved member of the tubulin superfamily with a function in microtubule nucleation. Proteins of γ-tubulin complexes serve as nucleation templates as well as a majority of other proteins contributing to centrosomal and non-centrosomal nucleation, conserved across eukaryotes. There is a growing amount of evidence of γ-tubulin functions besides microtubule nucleation in transcription, DNA damage response, chromatin remodeling, and on its interactions with tumor suppressors. However, the molecular mechanisms are not well understood. Furthermore, interactions with lamin and SUN proteins of the LINC complex suggest the role of γ-tubulin in the coupling of nuclear organization with cytoskeletons. γ-Tubulin that belongs to the clade of eukaryotic tubulins shows characteristics of both prokaryotic and eukaryotic tubulins. Both human and plant γ-tubulins preserve the ability of prokaryotic tubulins to assemble filaments and higher-order fibrillar networks. γ-Tubulin filaments, with bundling and aggregating capacity, are suggested to perform complex scaffolding and sequestration functions. In this review, we discuss a plethora of γ-tubulin molecular interactions and cellular functions, as well as recent advances in understanding the molecular mechanisms behind them. -
Lamin A/C Cardiomyopathy: Implications for Treatment
Current Cardiology Reports (2019) 21:160 https://doi.org/10.1007/s11886-019-1224-7 MYOCARDIAL DISEASE (A ABBATE AND G SINAGRA, SECTION EDITORS) Lamin A/C Cardiomyopathy: Implications for Treatment Suet Nee Chen1 & Orfeo Sbaizero1,2 & Matthew R. G. Taylor1 & Luisa Mestroni1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review The purpose of this review is to provide an update on lamin A/C (LMNA)-related cardiomyopathy and discuss the current recommendations and progress in the management of this disease. LMNA-related cardiomyopathy, an inherited autosomal dominant disease, is one of the most common causes of dilated cardiomyopathy and is characterized by steady progression toward heart failure and high risks of arrhythmias and sudden cardiac death. Recent Findings We discuss recent advances in the understanding of the molecular mechanisms of the disease including altered cell biomechanics, which may represent novel therapeutic targets to advance the current management approach, which relies on standard heart failure recommendations. Future therapeutic approaches include repurposed molecularly directed drugs, siRNA- based gene silencing, and genome editing. Summary LMNA-related cardiomyopathy is the focus of active in vitro and in vivo research, which is expected to generate novel biomarkers and identify new therapeutic targets. LMNA-related cardiomyopathy trials are currently underway. Keywords Lamin A/C gene . Laminopathy . Heart failure . Arrhythmias . Mechanotransduction . P53 . CRISPR–Cas9 therapy Introduction functions, including maintaining nuclear structural integrity, regulating gene expression, mechanosensing, and Mutations in the lamin A/C gene (LMNA)causelaminopathies, mechanotransduction through the lamina-associated proteins a heterogeneous group of inherited disorders including muscu- [6–11]. -
Lamin A/C: Function in Normal and Tumor Cells
cancers Review Lamin A/C: Function in Normal and Tumor Cells Niina Dubik and Sabine Mai * Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E0V9, Canada; [email protected] * Correspondence: [email protected] Received: 9 November 2020; Accepted: 8 December 2020; Published: 9 December 2020 Simple Summary: The aim of this review is to summarize lamin A/C’s currently known functions in both normal and diseased cells. Lamin A/C is a nuclear protein with many functions in cells, such as maintaining a cell’s structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere protection. Mutations of the lamin A/C gene, incorrect processing of the protein, and lamin A/C deregulation can lead to various diseases and cancer. This review touches on diseases caused by mutation and incorrect processing of lamin A/C, called laminopathies. The effect of lamin A/C deregulation in cancer is also reviewed, and lamin A/C’s potential in helping to diagnose prostate cancers more accurately is discussed. Abstract: This review is focused on lamin A/C, a nuclear protein with multiple functions in normal and diseased cells. Its functions, as known to date, are summarized. This summary includes its role in maintaining a cell’s structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere protection. As lamin A/C has a variety of critical roles within the cell, mutations of the lamin A/C gene and incorrect processing of the protein results in a wide variety of diseases, ranging from striated muscle disorders to accelerated aging diseases. -
Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations
Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations by Jelena Perovanovic M.S. in Molecular Biology and Physiology, September 2009, University of Belgrade M.Phil. in Molecular Medicine, August 2013, The George Washington University A Dissertation submitted to The Faculty of The Columbian College of Arts and Sciences of The George Washington University in partial fulfillment of the requirements for the degree of Doctor of Philosophy August 31, 2015 Dissertation directed by Eric P. Hoffman Professor of Integrative Systems Biology The Columbian College of Arts and Sciences of The George Washington University certifies that Jelena Perovanovic has passed the Final Examination for the degree of Doctor of Philosophy as of May 5, 2015. This is the final and approved form of the dissertation. Nuclear Envelope Laminopathies: Evidence for Developmentally Inappropriate Nuclear Envelope-Chromatin Associations Jelena Perovanovic Dissertation Research Committee: Eric P. Hoffman, Professor of Integrative Systems Biology, Dissertation Director Anamaris Colberg-Poley, Professor of Integrative Systems Biology, Committee Member Robert J. Freishtat, Associate Professor of Pediatrics, Committee Member Vittorio Sartorelli, Senior Investigator, National Institutes of Health, Committee Member ii © Copyright 2015 by Jelena Perovanovic All rights reserved iii Acknowledgments I am deeply indebted to countless individuals for their support and encouragement during the past five years of graduate studies. First and foremost, I would like to express my gratitude to my mentor, Dr. Eric P. Hoffman, for his unwavering support and guidance, and keen attention to my professional development. This Dissertation would not have been possible without the critical input he provided and the engaging environment he created. -
The Microtubule Poison Vinorelbine Kills Cells Independently of Mitotic Arrest and Targets Cells Lacking the APC Tumour Suppressor More Effectively
Research Article 887 The microtubule poison vinorelbine kills cells independently of mitotic arrest and targets cells lacking the APC tumour suppressor more effectively Daniel M. Klotz1, Scott A. Nelson1, Karin Kroboth2, Ian P. Newton1, Sorina Radulescu3, Rachel A. Ridgway3, Owen J. Sansom3, Paul L. Appleton1 and Inke S. Na¨thke1,* 1Division of Cell and Developmental Biology, 2Division of Molecular Medicine, University of Dundee, Dow Street, Dundee, DD1 5EH, UK 3The Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK *Author for correspondence ([email protected]) Accepted 28 September 2011 Journal of Cell Science 125, 887–895 ß 2012. Published by The Company of Biologists Ltd doi: 10.1242/jcs.091843 Summary Colorectal cancers commonly carry truncation mutations in the adenomatous polyposis coli (APC) gene. The APC protein contributes to the stabilization of microtubules. Consistently, microtubules in cells lacking APC depolymerize more readily in response to microtubule-destabilizing drugs. This raises the possibility that such agents are suitable for treatment of APC-deficient cancers. However, APC-deficient cells have a compromised spindle assembly checkpoint, which renders them less sensitive to killing by microtubule poisons whose toxicity relies on the induction of prolonged mitotic arrest. Here, we describe the novel discovery that the clinically used microtubule-depolymerizing drug vinorelbine (Navelbine) kills APC-deficient cells in culture and in intestinal tissue more effectively than it kills wild-type cells. This is due to the ability of vinorelbine to kill cells in interphase independently of mitotic arrest. Consistent with a role for p53 in cell death in interphase, depletion of p53 renders cells less sensitive to vinorelbine, but only in the presence of wild-type APC. -
Deficiencies in Lamin B1 and Lamin B2 Cause Neurodevelopmental Defects and Distinct Nuclear Shape Abnormalities in Neurons
M BoC | ARTICLE Deficiencies in lamin B1 and lamin B2 cause neurodevelopmental defects and distinct nuclear shape abnormalities in neurons Catherine Coffiniera, Hea-Jin Jungb, Chika Nobumoria, Sandy Changa, Yiping Tua, Richard H. Barnes IIa, Yuko Yoshinagac, Pieter J. de Jongc, Laurent Vergnesd, Karen Reued, Loren G. Fonga, and Stephen G. Younga,d aDepartment of Medicine and bMolecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095; cChildren’s Hospital Oakland Research Institute, Oakland, CA 94609; dDepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095 ABSTRACT Neuronal migration is essential for the development of the mammalian brain. Monitoring Editor Here, we document severe defects in neuronal migration and reduced numbers of neurons in Thomas Michael Magin lamin B1–deficient mice. Lamin B1 deficiency resulted in striking abnormalities in the nuclear University of Leipzig shape of cortical neurons; many neurons contained a solitary nuclear bleb and exhibited an Received: Jun 13, 2011 asymmetric distribution of lamin B2. In contrast, lamin B2 deficiency led to increased numbers Revised: Sep 9, 2011 of neurons with elongated nuclei. We used conditional alleles for Lmnb1 and Lmnb2 to create Accepted: Sep 23, 2011 forebrain-specific knockout mice. The forebrain-specificLmnb1- and Lmnb2-knockout models had a small forebrain with disorganized layering of neurons and nuclear shape abnormalities, similar to abnormalities identified in the conventional knockout mice. A more severe pheno- type, complete atrophy of the cortex, was observed in forebrain-specific Lmnb1/Lmnb2 double-knockout mice. This study demonstrates that both lamin B1 and lamin B2 are essential for brain development, with lamin B1 being required for the integrity of the nuclear lamina, and lamin B2 being important for resistance to nuclear elongation in neurons. -
Why Is Lamin B Receptor Downregulated in Senescence?
Advanced Techniques in Biology & Lukášová et al., Adv Tech Biol Med 2017, 5:3 Medicine DOI: 10.4172/2379-1764.1000237 Mini Review Open Access Why is Lamin B Receptor Downregulated in Senescence? Emilie Lukášová1*, Aleš Kovařík2 and Stanislav Kozubek1 1Department of Cell Biology and Radiobiology, Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno 61265, Czech Republic 2Deparrtment of Molecular Epigenetics, Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno 61265, Czech Republic *Corresponding author: Emilie Lukášová, Department of Cell Biology and Radiobiology, Institute of Biophysics, Czech Academy of Sciences, Královopolská 135, Brno 61265, Czech Republic, Tel: +420 - 541 517 157; E-mail: [email protected] Received date: July 19, 2017; Accepted date: August 03, 2017; Published date: August 10, 2017 Copyright: © 2017 Lukášová E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract An important mechanism ensuring spatial organization of chromatin structure and genome function in eukaryotic nuclei consists in anchoring of specific heterochromatin regions to nuclear envelope by proteins of inner nuclear membrane (INM) that are able to recognize these regions and simultaneously bind either Lamin A/C or lamin B1. One of these proteins is lamin B receptor (LBR) that binds lamin B1 and tethers heterochromatin to INM in embryonic and undifferentiated cells. It is replaced by lamin A/C with specific lamin A/C binding proteins (especially LEM-domain proteins) at the beginning of cell differentiation. -
Supplementary Table S4
Supplementary Table 4. Proteins with differentially regulated phosphopeptides corresponding to the cytoskeleton group according to DAVID GO analysis. Phosphopeptides corresponding to 91 different proteins were found differentially regulated and enriched in the cluster group cytoskeleton by GO analysis. Swissprot Accession numbers and Protein Names are listed. Swissprot Accession Protein Name 796257 A kinase (PRKA) anchor protein 12 805574 CAP, adenylate cyclase-associated protein 1 (yeast) 791903 CTTNBP2 N-terminal like 822287 DEAH (Asp-Glu-Ala-His) box polypeptide 9 811814 FERM domain containing 4A 776468 FK506 binding protein 15, 133kDa 789474 G protein-coupled receptor kinase interacting ArfGAP 1 779713 LIM domain and actin binding 1 825345 MAP7 domain containing 1 811248 MYC binding protein 2 817876 N-myc downstream regulated 1 795829 PDZ and LIM domain 7 (enigma) 774165 PTK2 protein tyrosine kinase 2 816535 Rho GTPase activating protein 21 818916 Rho/Rac guanine nucleotide exchange factor (GEF) 2 797168 SH3 and PX domains 2A 823031 SH3-domain kinase binding protein 1 800683 TPX2, microtubule-associated, homolog (Xenopus laevis) 782161 abl-interactor 1 794307 adducin 1 (alpha) 778958 adducin 3 (gamma) 805050 anillin, actin binding protein 788291 ankyrin 3, node of Ranvier (ankyrin G) 817614 annexin A1 815142 cell division cycle 2, G1 to S and G2 to M 824974 cell division cycle associated 8 824809 centrosomal protein 170kDa 803713 chromobox homolog 1 (HP1 beta homolog Drosophila ) 809850 chromosome 13 open reading frame 3 823922 cortactin