Microtubule Motors
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Unsheathing WASP's Sting
news and views required for Swallow-mediated localiza- Cytoplasmic dynein is implicated in Minneapolis 55455, Minnesota, USA tion within the oocyte. many biological processes, including ves- e-mail:[email protected] The interaction between Swallow and icle and organelle transport, mitotic- Roger Karess is at the CNRS Centre de Génétique Dlc is a significant finding and provides spindle function and orientation, and Moléculaire, Ave de la Terrasse, 91198 Gif-sur- the basis for a model in which the dynein- now RNA transport and localization. It is Yvette, France motor complex is responsible for the important to emphasize that a single iso- e-mail: [email protected] anterior localization of bicoid RNA within form of the dynein-motor subunit is 1. St Johnston, D. Cell 81, 167–170 (1995). the oocyte. Interestingly, the transient known to be targeted to several cellular 2. Bashirullah, A., Cooperstock, R. & Lipshitz, H. Annu. Rev. localization of Swallow to the oocyte functions and molecular cargoes within Biochem. 67, 335–394 (1998). anterior occurs at a time when most of the individual cells. Thus it is those molecules 3. Oleynikov, Y. & Singer, R. Trends Cell Biol. 8, 381–383 dynein-motor subunits are concentrated with adaptor functions, such as those pro- (1998). 13 4. Wilhelm, J. & Vale, R. J. Cell Biol. 123, 269–274 (1993). at the posterior of the oocyte . This raises posed here for Swallow, that must 5. Schnorrer, F., Bohmann, K. & Nusslein-Volhard, C. Nature Cell the possibility that at least two distinct account for the functional specificity of Biol. -
UCSD MOLECULE PAGES Doi:10.6072/H0.MP.A002549.01 Volume 1, Issue 2, 2012 Copyright UC Press, All Rights Reserved
UCSD MOLECULE PAGES doi:10.6072/H0.MP.A002549.01 Volume 1, Issue 2, 2012 Copyright UC Press, All rights reserved. Review Article Open Access WAVE2 Tadaomi Takenawa1, Shiro Suetsugu2, Daisuke Yamazaki3, Shusaku Kurisu1 WASP family verprolin-homologous protein 2 (WAVE2, also called WASF2) was originally identified by its sequence similarity at the carboxy-terminal VCA (verprolin, cofilin/central, acidic) domain with Wiskott-Aldrich syndrome protein (WASP) and N-WASP (neural WASP). In mammals, WAVE2 is ubiquitously expressed, and its two paralogs, WAVE1 (also called suppressor of cAMP receptor 1, SCAR1) and WAVE3, are predominantly expressed in the brain. The VCA domain of WASP and WAVE family proteins can activate the actin-related protein 2/3 (Arp2/3) complex, a major actin nucleator in cells. Proteins that can activate the Arp2/3 complex are now collectively known as nucleation-promoting factors (NPFs), and the WASP and WAVE families are a founding class of NPFs. The WAVE family has an amino-terminal WAVE homology domain (WHD domain, also called the SCAR homology domain, SHD) followed by the proline-rich region that interacts with various Src-homology 3 (SH3) domain proteins. The VCA domain located at the C-terminus. WAVE2, like WAVE1 and WAVE3, constitutively forms a huge heteropentameric protein complex (the WANP complex), binding through its WHD domain with Abi-1 (or its paralogs, Abi-2 and Abi-3), HSPC300 (also called Brick1), Nap1 (also called Hem-2 and NCKAP1), Sra1 (also called p140Sra1 and CYFIP1; its paralog is PIR121 or CYFIP2). The WANP complex is recruited to the plasma membrane by cooperative action of activated Rac GTPases and acidic phosphoinositides. -
Conserved Microtubule–Actin Interactions in Cell Movement and Morphogenesis
REVIEW Conserved microtubule–actin interactions in cell movement and morphogenesis Olga C. Rodriguez, Andrew W. Schaefer, Craig A. Mandato, Paul Forscher, William M. Bement and Clare M. Waterman-Storer Interactions between microtubules and actin are a basic phenomenon that underlies many fundamental processes in which dynamic cellular asymmetries need to be established and maintained. These are processes as diverse as cell motility, neuronal pathfinding, cellular wound healing, cell division and cortical flow. Microtubules and actin exhibit two mechanistic classes of interactions — regulatory and structural. These interactions comprise at least three conserved ‘mechanochemical activity modules’ that perform similar roles in these diverse cell functions. Over the past 35 years, great progress has been made towards under- crosstalk occurs in processes that require dynamic cellular asymme- standing the roles of the microtubule and actin cytoskeletal filament tries to be established or maintained to allow rapid intracellular reor- systems in mechanical cellular processes such as dynamic shape ganization or changes in shape or direction in response to stimuli. change, shape maintenance and intracellular organelle movement. Furthermore, the widespread occurrence of these interactions under- These functions are attributed to the ability of polarized cytoskeletal scores their importance for life, as they occur in diverse cell types polymers to assemble and disassemble rapidly, and to interact with including epithelia, neurons, fibroblasts, oocytes and early embryos, binding proteins and molecular motors that mediate their regulated and across species from yeast to humans. Thus, defining the mecha- movement and/or assembly into higher order structures, such as radial nisms by which actin and microtubules interact is key to understand- arrays or bundles. -
Phosphorylation of the Microtubule-Severing AAA+ Enzyme Katanin Regulates C
Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development Nicolas Joly, Eva Beaumale, Lucie van Hove, Lisa Martino, Lionel Pintard To cite this version: Nicolas Joly, Eva Beaumale, Lucie van Hove, Lisa Martino, Lionel Pintard. Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development. Journal of Cell Biology, Rockefeller University Press, 2020, 219 (6), 10.1083/jcb.201912037. hal-03011242 HAL Id: hal-03011242 https://hal.archives-ouvertes.fr/hal-03011242 Submitted on 18 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ARTICLE Phosphorylation of the microtubule-severing AAA+ enzyme Katanin regulates C. elegans embryo development Nicolas Joly, Eva Beaumale, Lucie Van Hove, Lisa Martino, and Lionel Pintard The evolutionarily conserved microtubule (MT)-severing AAA-ATPase enzyme Katanin is emerging as a critical regulator of MT dynamics. In Caenorhabditis elegans, Katanin MT-severing activity is essential for meiotic spindle assembly but is toxic for the Downloaded from https://rupress.org/jcb/article-pdf/219/6/e201912037/1044138/jcb_201912037.pdf by guest on 20 July 2020 mitotic spindle. Here we analyzed Katanin dynamics in C. elegans and deciphered the role of Katanin phosphorylation in the regulation of its activity and stability. -
Absence of NEFL in Patient-Specific Neurons in Early-Onset Charcot-Marie-Tooth Neuropathy Markus T
ARTICLE OPEN ACCESS Absence of NEFL in patient-specific neurons in early-onset Charcot-Marie-Tooth neuropathy Markus T. Sainio, MSc, Emil Ylikallio, MD, PhD, Laura M¨aenp¨a¨a, MSc, Jenni Lahtela, PhD, Pirkko Mattila, PhD, Correspondence Mari Auranen, MD, PhD, Johanna Palmio, MD, PhD, and Henna Tyynismaa, PhD Dr. Tyynismaa [email protected] Neurol Genet 2018;4:e244. doi:10.1212/NXG.0000000000000244 Abstract Objective We used patient-specific neuronal cultures to characterize the molecular genetic mechanism of recessive nonsense mutations in neurofilament light (NEFL) underlying early-onset Charcot- Marie-Tooth (CMT) disease. Methods Motor neurons were differentiated from induced pluripotent stem cells of a patient with early- onset CMT carrying a novel homozygous nonsense mutation in NEFL. Quantitative PCR, protein analytics, immunocytochemistry, electron microscopy, and single-cell transcriptomics were used to investigate patient and control neurons. Results We show that the recessive nonsense mutation causes a nearly total loss of NEFL messenger RNA (mRNA), leading to the complete absence of NEFL protein in patient’s cultured neurons. Yet the cultured neurons were able to differentiate and form neuronal networks and neuro- filaments. Single-neuron gene expression fingerprinting pinpointed NEFL as the most down- regulated gene in the patient neurons and provided data of intermediate filament transcript abundancy and dynamics in cultured neurons. Blocking of nonsense-mediated decay partially rescued the loss of NEFL mRNA. Conclusions The strict neuronal specificity of neurofilament has hindered the mechanistic studies of re- cessive NEFL nonsense mutations. Here, we show that such mutation leads to the absence of NEFL, causing childhood-onset neuropathy through a loss-of-function mechanism. -
Tracking Melanosomes Inside a Cell to Study Molecular Motors and Their Interaction
Tracking melanosomes inside a cell to study molecular motors and their interaction Comert Kural*, Anna S. Serpinskaya†, Ying-Hao Chou†, Robert D. Goldman†, Vladimir I. Gelfand†‡, and Paul R. Selvin*§¶ *Center for Biophysics and Computational Biology and §Department of Physics, University of Illinois at Urbana–Champaign, Urbana, IL 61801; and †Department of Cell and Molecular Biology, Northwestern University School of Medicine, Chicago, IL 60611 Communicated by Gordon A. Baym, University of Illinois at Urbana–Champaign, Urbana, IL, January 9, 2007 (received for review June 4, 2006) Cells known as melanophores contain melanosomes, which are membrane organelles filled with melanin, a dark, nonfluorescent pigment. Melanophores aggregate or disperse their melanosomes when the host needs to change its color in response to the environment (e.g., camouflage or social interactions). Melanosome transport in cultured Xenopus melanophores is mediated by my- osin V, heterotrimeric kinesin-2, and cytoplasmic dynein. Here, we describe a technique for tracking individual motors of each type, both individually and in their interaction, with high spatial (Ϸ2 nm) and temporal (Ϸ1 msec) localization accuracy. This method enabled us to observe (i) stepwise movement of kinesin-2 with an average step size of 8 nm; (ii) smoother melanosome transport (with fewer pauses), in the absence of intermediate filaments (IFs); and (iii) motors of actin filaments and microtubules working on the same cargo nearly simultaneously, indicating that a diffusive step is not needed between the two systems of transport. In concert with our previous report, our results also show that dynein-driven retro- grade movement occurs in 8-nm steps. Furthermore, previous studies have shown that melanosomes carried by myosin V move 35 nm in a stepwise fashion in which the step rise-times can be as long as 80 msec. -
Yuri Gagarin Is Required for Actin, Tubulin and Basal Body Functions in Drosophila Spermatogenesis
1926 Research Article yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis Michael J. Texada, Rebecca A. Simonette, Cassidy B. Johnson, William J. Deery and Kathleen M. Beckingham* Department of Biochemistry and Cell Biology, MS-140, Rice University, 6100 South Main Street, Houston, TX 77005, USA *Author for correspondence (e-mail: [email protected]) Accepted 20 March 2008 Journal of Cell Science 121, 1926-1936 Published by The Company of Biologists 2008 doi:10.1242/jcs.026559 Summary Males of the genus Drosophila produce sperm of remarkable the yuri mutant, late clusters of syncytial nuclei are deformed length. Investigation of giant sperm production in Drosophila and disorganized. The basal bodies are also mispositioned on melanogaster has demonstrated that specialized actin and the nuclei, and the association of a specialized structure, the microtubule structures play key roles. The gene yuri gagarin centriolar adjunct (CA), with the basal body is lost. Some of (yuri) encodes a novel protein previously identified through its these nuclear defects might underlie a further unexpected role in gravitaxis. A male-sterile mutation of yuri has revealed abnormality: sperm nuclei occasionally locate to the wrong ends roles for Yuri in the functions of the actin and tubulin structures of the spermatid cysts. The structure of the axonemes that grow of spermatogenesis. Yuri is a component of the motile actin cones out from the basal bodies is affected in the yuri mutant, that individualize the spermatids and is essential for their suggesting a possible role for the CA in axoneme formation. formation. Furthermore, Yuri is required for actin accumulation in the dense complex, a microtubule-rich structure on the sperm Key words: Drosophila, Spermatogenesis, Actin, Tubulin, Basal nuclei thought to strengthen the nuclei during elongation. -
Cytoplasmic Dynein Pushes the Cytoskeletal Meshwork Forward During Axonal Elongation
ß 2014. Published by The Company of Biologists Ltd | Journal of Cell Science (2014) 127, 3593–3602 doi:10.1242/jcs.152611 RESEARCH ARTICLE Cytoplasmic dynein pushes the cytoskeletal meshwork forward during axonal elongation Douglas H. Roossien1, Phillip Lamoureux2 and Kyle E. Miller2,* ABSTRACT were not a species-specific phenomenon, but rather a broadly conserved mechanism for elongation. From this, a new model for During development, neurons send out axonal processes that can axonal elongation has emerged, termed ‘stretch and intercalation’ reach lengths hundreds of times longer than the diameter of their (SAI) (Suter and Miller, 2011), in which forces cause the cell bodies. Recent studies indicate that en masse microtubule microtubule-rich central domain (C-domain) of the growth cone translocation is a significant mechanism underlying axonal to advance in bulk. This is paired with stretching of the axon, elongation, but how cellular forces drive this process is unknown. which is followed by intercalated mass addition along the axon Cytoplasmic dynein generates forces on microtubules in axons to to prevent thinning (Lamoureux et al., 2010). In terms of the power their movement through ‘stop-and-go’ transport, but whether cytoskeleton, stretching presumably occurs because filaments are these forces influence the bulk translocation of long microtubules sliding apart either through pulling or pushing forces generated embedded in the cytoskeletal meshwork has not been tested. by molecular motors (Suter and Miller, 2011; Lu et al., 2013; Here, we use both function-blocking antibodies targeted to Roossien et al., 2013). It is worth noting that because adhesions the dynein intermediate chain and the pharmacological dynein along the axon dissipate forces generated in the growth inhibitor ciliobrevin D to ask whether dynein forces contribute to en cone (O’Toole et al., 2008), these en masse movements of bloc cytoskeleton translocation. -
Deciphering the Role of a Microtubule Severing Protein and a Protein Kinase in Cell Cycle and Ciliogenesis in Chlamydomonas Reinhardtii
DECIPHERING THE ROLE OF A MICROTUBULE SEVERING PROTEIN AND A PROTEIN KINASE IN CELL CYCLE AND CILIOGENESIS IN CHLAMYDOMONAS REINHARDTII by M. Qasim Rasi B.Sc., Simon Fraser University, 2004 THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY In the Department of Molecular Biology and Biochemistry ©M. Qasim Rasi 2009 SIMON FRASER UNIVERSITY Summer 2009 All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author APPROVAL Name: M. Qasim Rasi Degree: Doctor of Philosophy Title of Thesis: Deciphering the role of a microtubule severing protein and a protein kinase in cell cycle and ciliogenesis in Chlamydomonas reinhardtii Examining Committee: Chair: Dr. C. Krieger Professor of Kinesiology _______________________________________________ Dr. Lynne Quarmby Senior Supervisor; Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Michel Leroux Supervisor; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Nick Harden Supervisor; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Christopher Beh Internal Examiner; Associate Professor of Molecular Biology and Biochemistry _______________________________________________ Dr. Stephen M. King External Examiner; Professor of Biochemistry, Associate Director, Graduate Program in Molecular Biology and Biochemistry, University of Connecticut Health Center Date Defended/Approved: June-5-2009 ii Declaration of Partial Copyright Licence The author, whose copyright is declared on the title page of this work, has granted to Simon Fraser University the right to lend this thesis, project or extended essay to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational institution, on its own behalf or for one of its users. -
The Kinesin Walk: a Dynamic Model with Elastically Coupled Heads
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 6775-6779, June 1996 Biophysics The kinesin walk: A dynamic model with elastically coupled heads IMRE DERENYI AND TAMA'S VICSEK Department of Atomic Physics, Eotvos University, Budapest, Puskin u 5-7, 1088 Hungary Communicated by Leo P. Kadanoff, University of Chicago, Chicago, IL, February 26, 1996 (received for review November 28, 1995) ABSTRACT Recently individual two-headed kinesin mol- of the related transport phenomena. These models (12-19), ecules have been studied in in vitro motility assays revealing a except that of Ajdari (20), consider cases in which the internal number of their peculiar transport properties. In this paper degree of freedom of the molecular motors is not taken into we propose a simple and robust model for the kinesin stepping account. The purpose of the present work is to define and process with elastically coupled Brownian heads that show all investigate a dynamic model for the kinesin walk that has an of these properties. The analytic and numerical treatment of internal degree of freedom and results in a full agreement with our model results in a very good fit to the experimental data the experimental data for the range of its parameters allowed and practically has no free parameters. Changing the values by the known estimates for the lower and upper bounds of ofthe parameters in the restricted range allowed by the related these parameters. experimental estimates has almost no effect on the shape of There are two basic classes of possible models for the the curves and results mainly in a variation of the zero load stepping of kinesin (21). -
Kinesin Motility Is Driven by Subdomain Dynamics Wonmuk Hwang1,2,3*, Matthew J Lang4,5*, Martin Karplus6,7*
RESEARCH ARTICLE Kinesin motility is driven by subdomain dynamics Wonmuk Hwang1,2,3*, Matthew J Lang4,5*, Martin Karplus6,7* 1Department of Biomedical Engineering, Texas A&M University, College Station, United States; 2Department of Materials Science & Engineering, Texas A&M University, College Station, United States; 3School of Computational Sciences, Korea Institute for Advanced Study, Seoul, Korea; 4Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, United States; 5Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States; 6Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States; 7Laboratoire de Chimie Biophysique, ISIS, Universite´ de Strasbourg, Strasbourg, France Abstract The microtubule (MT)-associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics. Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle, the atomic mechanism of the core events remain to be found. To obtain insights into the mechanism, we performed 38.5 microseconds of all-atom molecular dynamics simulations of kinesin-MT complexes in different nucleotide states. Local subdomain dynamics were found to be essential for nucleotide processing. Catalytic water molecules are dynamically organized by the switch domains of the nucleotide binding pocket while ATP is torsionally strained. Hydrolysis products are ’pulled’ by switch-I, and a new ATP is ’captured’ by a concerted motion of the a0/L5/switch-I trio. The dynamic and wet kinesin-MT interface is tuned for rapid interactions while maintaining specificity. The proposed *For correspondence: mechanism provides the flexibility necessary for walking in the crowded cellular environment. [email protected] (WH); DOI: https://doi.org/10.7554/eLife.28948.001 [email protected] (MJL); [email protected] (MK) Competing interests: The authors declare that no Introduction competing interests exist. -
Microtubule-Associated Protein Tau (Molecular Pathology/Neurodegenerative Disease/Neurofibriliary Tangles) M
Proc. Nati. Acad. Sci. USA Vol. 85, pp. 4051-4055, June 1988 Medical Sciences Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: Identification as the microtubule-associated protein tau (molecular pathology/neurodegenerative disease/neurofibriliary tangles) M. GOEDERT*, C. M. WISCHIK*t, R. A. CROWTHER*, J. E. WALKER*, AND A. KLUG* *Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom; and tDepartment of Psychiatry, University of Cambridge Clinical School, Hills Road, Cambridge CB2 2QQ, United Kingdom Contributed by A. Klug, March 1, 1988 ABSTRACT Screening of cDNA libraries prepared from (21). This task is made all the more difficult because there is the frontal cortex ofan zheimer disease patient and from fetal no functional or physiological assay for the protein(s) of the human brain has led to isolation of the cDNA for a core protein PHF. The only identification so far possible is the morphol- of the paired helical fiament of Alzheimer disease. The partial ogy of the PHFs at the electron microscope level, and here amino acid sequence of this core protein was used to design we would accept only experiments on isolated individual synthetic oligonucleotide probes. The cDNA encodes a protein of filaments, not on neurofibrillary tangles (in which other 352 amino acids that contains a characteristic amino acid repeat material might be occluded). One thus needs a label or marker in its carboxyl-terminal half. This protein is highly homologous for the PHF itself, which can at the same time be used to to the sequence ofthe mouse microtubule-assoiated protein tau follow the steps of the biochemical purification.