Posttranslational Modification and Microtubule Stability Eric Schulze,* David J
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Regulation of Cardiovascular Homeostasis by Autophagy
Georgia State University ScholarWorks @ Georgia State University Chemistry Dissertations Department of Chemistry 12-16-2020 Regulation Of Cardiovascular Homeostasis By Autophagy Jing Mu Georgia State University Follow this and additional works at: https://scholarworks.gsu.edu/chemistry_diss Recommended Citation Mu, Jing, "Regulation Of Cardiovascular Homeostasis By Autophagy." Dissertation, Georgia State University, 2020. https://scholarworks.gsu.edu/chemistry_diss/190 This Dissertation is brought to you for free and open access by the Department of Chemistry at ScholarWorks @ Georgia State University. It has been accepted for inclusion in Chemistry Dissertations by an authorized administrator of ScholarWorks @ Georgia State University. For more information, please contact [email protected]. REGULATION OF CARDIOVASCULAR HOMEOSTASIS BY AUTOPHAGY by JING MU Under the Direction of Ming-hui Zou, MD/PhD ABSTRACT Macroautophagy (hereafter autophagy) is a fundamental cellular process that removes unnecessary or dysfunctional components. It allows the orderly degradation and recycling of cellular components. Mitophagy refers to the selective removal of damaged mitochondria via autophagy pathway. In addition to utilizing core autophagic machinery components, mitophagy exploits a variety of molecules, such as PTEN-induced putative kinase protein 1 (PINK1) and Parkin, to identify and eliminate damaged or superfluous mitochondria. Dysregulation of autophagy and mitophagy contributes to a variety of human disorders, including cardiovascular diseases, such as atherosclerosis and diabetic cardiomyopathy. Vascular smooth muscle cells (VSMCs) are a major component of the vascular media, and are vital for maintaining vessel homeostasis. Migration of VSMCs from the media to intima occurs during the development of atherosclerosis. Although alterations in autophagy activity have been reported in atherosclerosis, further investigation is required to delineate the mechanism by which autophagy regulates microtubule stability and cell migration. -
Beyond Darwin: Evolvability and the Generation of Novelty Marc Kirschner
Kirschner M BMC Biology 2013, 11:110 http://www.biomedcentral.com/1741-7007/11/110 INTERVIEW Open Access Beyond Darwin: evolvability and the generation of novelty Marc Kirschner Marc Kirschner graduated in biochemistry from North- western University, moving to Berkeley for his doctoral research and with positions at Berkeley, Oxford Univer- sity and Princeton before he took a professorship at Uni- versity of California San Francisco where with Andrew Murray he did seminal research on the control of the cell cycle in Xenopus egg extracts that led to the discov- ery of how cyclin drives the cell cycle, and with Tim Mitchison on the dynamic instability of microtubules. In 1993 he moved to Harvard where in 2003 he became the founding Chair of the HMS Department of Systems Biology and was named the John Franklin Enders Uni- versity Professor in 2009. The two books he wrote with John Gerhart, Cells, Embryos and Evolution (Blackwell, 1997) and The Plausibility of Life: Resolving Darwin’sDi- lemma (Yale University Press, 2005), reflect his deep and longstanding interest in how biological systems evolve. Here he gives his view of the evolution of evolvability and its profound importance for understanding and ap- plying biology. What is evolvability - how would you define it? Marc Kirschner In some sort of tautological way evolvability is simply the capacity of a system to evolve. But more than that, in a Darwinian sense it speaks to both the amount of effectively what I mean is that if you make random variation that is subject to selection, and the nature of changes in mechanical systems they inevitably either that variation. -
Dissertation Kokes M
Mechanisms of Chlamydia Manipulation of Host Cell Biology Revealed Through Genetic Approaches by Marcela Kokes Department of Molecular Genetics and Microbiology Program in Cell and Molecular Biology Duke University Date:_______________________ Approved: ___________________________ Raphael H. Valdivia, Supervisor ___________________________ Daniel J. Lew ___________________________ Jörn Coers ___________________________ Patrick C. Seed Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Molecular Genetics and Microbiology in the Graduate School of Duke University 2015 i v ABSTRACT Mechanisms of Chlamydia Manipulation of Host Cell Biology Revealed Through Genetic Approaches by Marcela Kokes Department of Molecular Genetics and Microbiology Program in Cell and Molecular Biology Duke University Date:_______________________ Approved: ___________________________ Raphael H. Valdivia, Supervisor ___________________________ Daniel J. Lew ___________________________ Jörn Coers ___________________________ Patrick C. Seed An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Molecular Genetics and Microbiology in the Graduate School of Duke University 2015 Copyright by Marcela Kokes 2015 i v Abstract Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and is the leading cause of preventable blindness worldwide. Chlamydia is particularly intriguing from the perspective of cell biology because it is an obligate intracellular pathogen that manipulates host cellular pathways to ensure its proliferation and survival. This is achieved through a significant remodeling of the host cell’s internal architecture from within a membrane-bound vacuole, termed the inclusion. However, given a previous lack of tools to perform genetic analysis, the mechanisms by which Chlamydia induces host cellular changes remained unclear. -
Chromatography Including Electrophoresis and Other Separation Methods
15SIO 06£ i 36 j 6 VOL. 610 NO.2 JUNE 12, 1992 THIS ISSUE COMPLETES VOL. 610 Bibliography Section JOURNAL OF CHROMATOGRAPHY INCLUDING ELECTROPHORESIS AND OTHER SEPARATION METHODS EDITORS U. A. Th. Brinkman (Amsterdam) R. W. Giese (Boston, MA) J. K. Haken (Kensington, N.S.W.) K. Macek (Prague) L. R. Snyder (Orinda, CA) EDITORS. SYMPOSIUM VOLUMES. E. Heftmann (Orinda. CAl. Z. Deyl (Prague) EDITORIAL BOARD D. W. Armstrong (Rollo. MO) W. A. Aue (Holifo,) P. Botek (8.00) A. A. Boulton (Saskatoon) P. W. Cmr (Minneopolis. MN) N. H. C. Cooke (San Ramon. CAl V. A. Davankov (Moscow) Z. Deyl (Progue) S. Dilli (Kl~nsington. N.S.W.) F. Ern! (Basle) M. B. Evans (Hatfield) J. L. Glojcl, (N. Billerico. MA) G. A. Guiochon (Knoxville, TN) P. R. Haddod (Kensington. N.S.W.) I. M. Hais (Hradec Kralove) W. S. Hancock (San FranCISCo. CAl S. Hjerten (Uppsalo) Cs. Horvinh (New Haven. CT) J. F. K. Huber (Vienna) K.·P. Hupe (Woldbronn) T. W. Hutchens (Houston. IX) J. Jonak (B.oo) P. Jandera (Pardubice) B. L. Kmger (B05<on. MA) J. J. Kirkland (Wilmington. DE) E. sz. Kovats (Lausanne) A. J. P. Mortin (Cambridge) L. W. McLoughlin (Chestnut Hill. MA) E. D. Morgan (Keele) J. O. Pearson (KrJlamazoo, MI) H. Poppe (Amsterdam) F. E. Regnier (West Lafayette. IN) P. G. Righetti (Milan) P. Sclloenmakers (Eindhoven) R. Schwarzenbach (Dubendor!) R. E. Shoup (West Lafayette. IN) A. M. Siouf!i (Mo,seille) D. J. Strydom (Boston. MA) N. Tonaka (Kyoto) S. Terabe (Hyogo) K. K. Unger (Mainz) R. Verpoorle (Leiden) Gy. -
The Drosophila MCPH1-B Isoform Is a Substrate of the APC E3 Ubiquitin Ligase Complex
ß 2014. Published by The Company of Biologists Ltd | Biology Open (2014) 3, 669–676 doi:10.1242/bio.20148318 RESEARCH ARTICLE The Drosophila MCPH1-B isoform is a substrate of the APCCdh1 E3 ubiquitin ligase complex Sarah G. Hainline`, Jamie L. Rickmyre`,*, Leif R. Neitzel, Laura A. Lee§ and Ethan Lee§ ABSTRACT and two primary co-activators, Cdc20 and Cdh1 (Kulkarni et al., 2013). Destruction of APC substrates is required in eukaryotes for The Anaphase-Promoting Complex (APC) is a multi-subunit E3 the initiation of anaphase and exit from mitosis. Cdc20 associates ubiquitin ligase that coordinates progression through the cell cycle by with the APC in early mitosis, leading to the destruction of temporally and spatially promoting the degradation of key proteins. proteins that control the onset of anaphase, whereas Cdh1 Many of these targeted proteins have been shown to play important promotes degradation of APC substrates that control late mitosis roles in regulating orderly progression through the cell cycle. Using and the following G1 phase. These co-activators provide APC a previously described Drosophila in vitro expression cloning substrate specificity by facilitating the recognition of specific approach, we screened for new substrates of the APC in Xenopus destruction motifs (e.g. degrons) such as the D-box (RxxLxxxxN) egg extract and identified Drosophila MCPH1 (dMCPH1), a protein or KEN box (Lys–Glu–Asn) (King et al., 1996; Min and Lindon, encoded by the homolog of a causative gene for autosomal recessive 2012; Pfleger and Kirschner, 2000). Mutations of these motifs primary microcephaly in humans. The dMCPH1-B splice form, but not block the recognition of the protein by the APC, preventing their the dMCPH1-C splice form, undergoes robust degradation in APC-mediated destruction. -
Rho Guanosine Triphosphatase Mediates the Selective Stabilization of Microtubules Induced by Lysophosphatidic Acid Tiffani A
Rho Guanosine Triphosphatase Mediates the Selective Stabilization of Microtubules Induced by Lysophosphatidic Acid Tiffani A. Cook,*‡ Takayuki Nagasaki,* and Gregg G. Gundersen*i *Department of Anatomy and Cell Biology, ‡Integrated Program in Cellular, Molecular, and Biophysical Studies, and iDepartment of Pathology, Columbia University, New York Abstract. The asymmetric distribution of stable, post- MTs and, in wound-edge cells, these stable MTs were translationally modified microtubules (MTs) contrib- appropriately oriented toward the leading edge of the utes to the polarization of many cell types, yet the fac- cell. LPA had little effect on individual parameters of tors controlling the formation of these MTs are not MT dynamics, but did induce long states of pause in a known. We have found that lysophosphatidic acid subset of MTs near the edge of the cell. Rho stimula- (LPA) is a major serum factor responsible for rapidly tion of MT stability was independent of actin stress fi- Downloaded from generating stable, detyrosinated (Glu) MTs in serum- ber formation. These results identify rho as a novel reg- starved 3T3 cells. Using C3 toxin and val14 rho we ulator of the MT cytoskeleton that selectively stabilizes showed that rho was both necessary and sufficient for MTs during cell polarization by acting as a switch be- the induction of Glu MTs by LPA and serum. Unlike tween dynamic and stable states of MTs rather than as previously described factors that induce MT stability, a modulator of MT assembly and disassembly. rho induced the stabilization of only a subset of the jcb.rupress.org n many cells there are at least two populations of mi- et al., 1984, 1987; Gundersen and Bulinski, 1986; Webster crotubules (MTs)1 distinguishable by their rates of et al., 1987; Kreis, 1987) and/or acetylated tubulin (Pip- on November 19, 2017 I turnover. -
Deptbiochemistry00ruttrich.Pdf
'Berkeley University o'f California Regional Oral History Office UCSF Oral History Program The Bancroft Library Department of the History of Health Sciences University of California, Berkeley University of California, San Francisco The UCSF Oral History Program and The Program in the History of the Biological Sciences and Biotechnology William J. Rutter, Ph.D. THE DEPARTMENT OF BIOCHEMISTRY AND THE MOLECULAR APPROACH TO BIOMEDICINE AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO VOLUME I With an Introduction by Lloyd H. Smith, Jr., M.D. Interviews by Sally Smith Hughes, Ph.D. in 1992 Copyright O 1998 by the Regents of the University of California Since 1954 the Regional Oral History Office has been interviewing leading participants in or well-placed witnesses to major events in the development of Northern California, the West, and the Nation. Oral history is a method of collecting historical information through tape-recorded interviews between a narrator with firsthand knowledge of historically significant events and a well- informed interviewer, with the goal of preserving substantive additions to the historical record. The tape recording is transcribed, lightly edited for continuity and clarity, and reviewed by the interviewee. The corrected manuscript is indexed, bound with photographs and illustrative materials, and placed in The Bancroft Library at the University of California, Berkeley, and in other research collections for scholarly use. Because it is primary material, oral history is not intended to present the final, verified, or complete narrative of events. It is a spoken account, offered by the interviewee in response to questioning, and as such it is reflective, partisan, deeply involved, and irreplaceable. -
Microtubule Acetylation but Not Detyrosination Promotes Focal
© 2019. Published by The Company of Biologists Ltd | Journal of Cell Science (2019) 132, jcs225805. doi:10.1242/jcs.225805 SHORT REPORT Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and astrocyte migration Bertille Bance1,2,*, Shailaja Seetharaman1,3,*, Cécile Leduc1, Batiste Boëda1 and Sandrine Etienne-Manneville1,‡ ABSTRACT Kaverina et al., 2002; Palazzo et al., 2004; Ezratty et al., 2009; Microtubules play a crucial role in mesenchymal migration by Stehbens et al., 2014). The polarized regulation of integrin-based controlling cell polarity and the turnover of cell adhesive structures on structures implies that the functions of microtubules must be the extracellular matrix. The polarized functions of microtubules imply controlled in a polarized manner. that microtubules are locally regulated. Here, we investigated the Several mechanisms, including MAP interactions and post- α β regulation and role of two major tubulin post-translational modifications, translational modifications of -and -tubulin (Janke, 2014; Song acetylation and detyrosination, which have been associated with stable and Brady, 2015; Etienne-Manneville, 2010; Strzyz, 2016; Aillaud microtubules. Using primary astrocytes in a wound healing assay, we et al., 2016), affect microtubule dynamics or microtubule association show that these tubulin modifications are independently regulated with protein partners (Janke, 2014; Raunser and Gatsogiannis, 2015; α during cell polarization and differently affect cell migration. In contrast to Yu et al., 2015; Song and Brady, 2015). TAT1 [also known as microtubule detyrosination, αTAT1 (ATAT1)-mediated microtubule ATAT1, and as Mec-17 in Caenorhabditis elegans (Akella et al., acetylation increases in the vicinity of focal adhesions and promotes 2010)] is the major tubulin acetyltransferase in mammals. -
The Tubulin Code and Its Role in Controlling Microtubule Properties and Functions
REVIEWS The tubulin code and its role in controlling microtubule properties and functions Carsten Janke 1,2 ✉ and Maria M. Magiera 1,2 ✉ Abstract | Microtubules are core components of the eukaryotic cytoskeleton with essential roles in cell division, shaping, motility and intracellular transport. Despite their functional heterogeneity , microtubules have a highly conserved structure made from almost identical molecular building blocks: the tubulin proteins. Alternative tubulin isotypes and a variety of post- translational modifications control the properties and functions of the microtubule cytoskeleton, a concept known as the ‘tubulin code’. Here we review the current understanding of the molecular components of the tubulin code and how they impact microtubule properties and functions. We discuss how tubulin isotypes and post-translational modifications control microtubule behaviour at the molecular level and how this translates into physiological functions at the cellular and organism levels. We then go on to show how fine-tuning of microtubule function by some tubulin modifications can affect homeostasis and how perturbation of this fine- tuning can lead to a range of dysfunctions, many of which are linked to human disease. 20 Axonemes Microtubules are cytoskeletal filaments with an outer cellular structures . Other MAPs bind to the micro- A tubular structure built from diameter of approximately 25 nm, and are composed of tubule lattice along its entire length and are thus con- microtubules and associated heterodimers of globular α- tubulin and β- tubulin mol- sidered to regulate microtubule dynamics and stability, proteins at the core of all ecules. As they are hollow cylinders, microtubules are but might also have additional roles that in many cases eukaryotic cilia and flagella. -
Cap-Gly Proteins at Microtubule Plus Ends: Is EB1 Detyrosination Involved?
Cap-Gly Proteins at Microtubule Plus Ends: Is EB1 Detyrosination Involved? Anouk Bosson, Jean-Marc Soleilhac, Odile Valiron, Didier Job, Annie Andrieux, Marie-Jo Moutin* Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) U836, Grenoble Institut des Neurosciences, Commissariat a` l’Energie Atomique (CEA) Institut de Recherches en Technologies et Sciences pour le Vivant - Groupe Physiopathologie du Cytosquelette (iRTSV-GPC), Universite´ Joseph Fourier, Grenoble, France Abstract Localization of CAP-Gly proteins such as CLIP170 at microtubule+ends results from their dual interaction with a-tubulin and EB1 through their C-terminal amino acids 2EEY. Detyrosination (cleavage of the terminal tyrosine) of a-tubulin by tubulin- carboxypeptidase abolishes CLIP170 binding. Can detyrosination affect EB1 and thus regulate the presence of CLIP170 at microtubule+ends as well? We developed specific antibodies to discriminate tyrosinated vs detyrosinated forms of EB1 and detected only tyrosinated EB1 in fibroblasts, astrocytes, and total brain tissue. Over-expressed EB1 was not detyrosinated in cells and chimeric EB1 with the eight C-terminal amino acids of a-tubulin was only barely detyrosinated. Our results indicate that detyrosination regulates CLIPs interaction with a-tubulin, but not with EB1. They highlight the specificity of carboxypeptidase toward tubulin. Citation: Bosson A, Soleilhac J-M, Valiron O, Job D, Andrieux A, et al. (2012) Cap-Gly Proteins at Microtubule Plus Ends: Is EB1 Detyrosination Involved? PLoS ONE 7(3): e33490. doi:10.1371/journal.pone.0033490 Editor: Thierry Soldati, Universite´ de Gene`ve, Switzerland Received November 18, 2011; Accepted February 15, 2012; Published March 14, 2012 Copyright: ß 2012 Bosson et al. -
Microtubule Tyrosination/Detyrosination Specifies a Mitotic Error Code
bioRxiv preprint doi: https://doi.org/10.1101/801977; this version posted October 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Microtubule tyrosination/detyrosination specifies a mitotic error code Luísa T. Ferreira1,2, Bernardo Orr1,2, Girish Rajendraprasad3, António J. Pereira1,2, Carolina Lemos2,4,5, Joana T. Lima1,2, Clàudia Guasch Boldú3, Jorge G. Ferreira1,2,6, Marin Barisic3,7, Helder Maiato1,2,6* 1 Chromosome Instability & Dynamics Group, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal 2 Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal 3 Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Strandboulevarden 49, 2100 Copenhagen, Denmark 4 UnIGENe, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal 5 Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal 6 Cell Division Group, Experimental Biology Unit, Department of Biomedicine, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal 7 Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark *Correspondence to: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/801977; this version posted October 11, 2019. -
Post-Translational Modifications Regulate Microtubule Function
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by MPG.PuRe REVIEWS POST-TRANSLATIONAL MODIFICATIONS REGULATE MICROTUBULE FUNCTION Stefan Westermann* and Klaus Weber ‡ The αβ-tubulin heterodimer, the building block of microtubules, is subject to a large number of post-translational modifications, comparable in diversity to the intensively studied histone modifications. Although these unusual modifications are conserved throughout evolution, their functions have remained almost completely elusive. Recently, however, important advances in the understanding of how tubulin modifications regulate function and organization have been made. αβ MITOTIC SPINDLE Microtubules are an important component of the domain of -tubulins, which is located on the outside 3 A bipolar array of microtubules cytoskeleton and carry out a variety of essential func- of the microtubule where it is well positioned to influ- that functions to move the tions. During cell division, microtubules form the ence interactions with other proteins. duplicated chromosomes MITOTIC SPINDLE, the structure that is required to faith- Here,we review the literature on the occurrence of during mitosis and meiosis. fully segregate replicated sister chromatids. Together these modifications, the enzymes that are involved in AXONEME with accessory proteins, they constitute the AXONEME of generating them, and their potential functions. A bundle of microtubules and CILIA and FLAGELLA and so contribute to cell motility. In associated proteins that form the addition, they are important factors in the generation The role of the tubulin tails core of a flagellum or cilium. of cell polarity and also function as tracks along which Electron crystallographic studies of the αβ-tubulin CILIA — with the help of motor proteins — organelles and dimer have provided important insights into its struc- Hair-like extensions of cells, vesicles are transported through the cell.