DOCSLIB.ORG

The Role of Calcium Flux in the Regulation of Filopodia Dynamics

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Role of Calcium Flux in the Regulation of Filopodia Dynamics THE ROLE OF CALCIUM FLUX IN THE REGULATION OF FILOPODIA DYNAMICS Omolade Ademuyiwa A Thesis Submitted to the Graduate College of Bowling Green State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE August 2019 Committee: Carol Heckman, Advisor Michael Geusz David Giovannucci © 2019 Omolade Ademuyiwa All Rights Reserved iii ABSTRACT Carol Heckman, Advisor Filopodia are finger-like projections on cells that allow the cells to sense and explore their external microenvironment. They are required for cell migration, neurogenesis and several other physiological processes. Filopodia dynamics have been widely studied in nerve cells. Here, I investigated the role of increased cytoplasmic calcium levels in the regulation of filopodia through activation of store-operated calcium entry in epithelial cells. The depletion of the endoplasmic reticulum store caused a transient increase in filopodia. The increase in fraction of cells with filopodia and percentage coverage of filopodia was seen at 10 min followed by a decrease at 30 min of treatment with cyclopiazonic acid (CPA). Filopodia dynamics are more sensitive to and regulated by Transient receptor potential cation (TRPC) channels. The downstream effectors of calcium such as calpain and calmodulin are negative regulators of filopodia. The possible mechanisms by which calcium regulates filopodia through these downstream effectors were reported here. The effect of calcium-like protein 2 (CALP2) in filopodia dynamics was first described in this study. iv To my parents, Chief A.S.A. Ademuyiwa and Mrs. Adenike Adetoye-Ademuyiwa v ACKNOWLEDGMENTS My sincere gratitude goes to my advisor, Dr. Carol Heckman. Thank you for standing by me every step of the way towards this achievement. This would not have been possible without you. I appreciate your guidance and for giving me the opportunity to work in your lab. You are like a mother to me and I pray for you this day that God will reward you and create a special place for you in Heaven because you are Heaven sent. I want to thank Dr. Cayer for showing me the ropes in the lab. I have learned so much in the past 2 years and I have you to thank for it. I will also like to thank my committee, Dr Michael Geusz and Dr. David Giovannucci for your guidance and for always ready to render your assistance when needed. In addition, Katie, Blair, Robyn and Nicole, thank you for all your help with filopodia counts. I will like to thank Bowling Green State University for my assistantship and general support. Lastly, I will like to thank my parents. Daddy thank you for my upbringing. I hope you are proud of me in heaven. May you continue to rest in the bosom of the Lord. Mummy, thank you for your infinite prayers and for always encouraging me to be the best I can be. vi TABLE OF CONTENTS Page CHAPTER ONE. INTRODUCTION ................................................................................ 1 1.1 Filopodia structure and formation ..................................................................... 1 1.2 Structural components of filopodia ................................................................... 5 1.2.1 Actin filaments .................................................................................. 5 1.2.2 Ena/VASP and Mena ......................................................................... 7 1.2.3 Small GTPases and their effectors ...................................................... 8 1.2.4 Wiskott-Aldrich syndrome protein (WASP) ....................................... 9 1.2.5 Fascin ................................................................................................ 9 1.2.6 Myosin-X .......................................................................................... 9 1.3 Filopodia regulation ......................................................................................... 12 1.3.1 Integrins............................................................................................. 12 1.3.2 Protein kinase C (PKC) ...................................................................... 13 1.4 Calcium signaling effect on filopodia formation ............................................... 14 1.4.1 Calcium in the body ........................................................................... 14 1.4.2 Calcium concentration needed for physiological processes ................. 14 1.4.3 Calcium signaling .............................................................................. 14 1.4.4 Intracellular store depletion ................................................................ 15 1.4.5 Downstream effectors of calcium ....................................................... 17 1.4.5.1 Calmodulin (CaM) .............................................................. 17 1.4.5.2 Calmodulin kinase (CaMK) ................................................. 18 1.4.5.3 Calpain ................................................................................ 20 vii 1.4.5.4 Calcineurin .......................................................................... 20 1.5 Calcium-filopodia relationship ......................................................................... 20 1.5.1 Calcium channel effects on filopodia formation ................................. 23 1.6 Aims and objectives ......................................................................................... 23 1.7 Hypothesis ....................................................................................................... 24 1.8 Significance of the study .................................................................................. 24 CHAPTER TWO. MATERIALS AND METHODS .......................................................... 25 2.1 Cell culture....................................................................................................... 25 2.1.1 Germanium (Ge) substrates for cell culture ........................................ 25 2.2 Calcium store depletion and replenishment ....................................................... 25 2.3 Chemical treatment and fixation ....................................................................... 26 2.3.1 Fixation ............................................................................................. 26 2.4 Filopodia determination.................................................................................... 27 2.5 Relative changes in calcium concentration ....................................................... 27 2.6 Statistical analysis ............................................................................................ 28 CHAPTER THREE. RESULTS........................................................................................ 29 3.1 Effect of ER depletion on filopodia formation .................................................. 29 3.1.2 Effect of ER stress causes an increase in calcium ............................... 31 3.2 Effect of calcium influx after store depletion on filopodia ................................ 35 3.2.1 Role of calcium channels in the regulation of filopodia ...................... 35 3.2.1.1 TRPC .................................................................................. 35 3.2.1.2 Orai ..................................................................................... 35 3.2.1.3 VGCC ................................................................................. 36 viii 3.3 Effect of downstream effectors of Calcium on filopodia regulation................... 40 3.3.1 Calpain .............................................................................................. 40 3.3.2 Calcineurin ........................................................................................ 40 3.3.3 CaMKII ............................................................................................. 40 3.3.4 CaM................................................................................................... 41 CHAPTER FOUR. DISCUSSION .................................................................................... 44 4.1 Increased cytoplasmic calcium regulates filopodia............................................ 44 4.2 Calcium influx through TRPC channel may be important in filopodia regulation ............................................................................................................... 46 4.3 The role of downstream effectors of calcium in the regulation of filopodia ....... 49 REFERENCES .................................................................................................................. 52 ix LIST OF FIGURES Figure Page 1 Architectural arrangement of filopodia in neurons .................................................. 2 2 GFP-actin time-lapse images showing stages of filopodia dynamics during dorsal closure at two-minute intervals ............................................................................... 4 3 Actin filament assembly and disassembly in filopodia ............................................ 6 4 Filopodia formation and elongation stages during cell migration ............................ 10 5 Structure of integrin and its subunits ...................................................................... 12 6 Main paths of calcium flux ..................................................................................... 16 7 ER depletion effect on filopodia dynamics ............................................................. 30 8 Hypothetical interpretation of time course .............................................................. 32 9 Increase in
Load more

Recommended publications
  • 4 Mechanics of the Cytoskeleton
    4 Mechanics of the cytoskeleton 4.1 Motivation In the previous section, we have seen how biopolymers dynamically assemble and dis- assemble during polymerization. We have discussed the individual mechanical prop- erties such as Young’s modulus E, the axial stiffness EA, the bending stiffness EI, and the persistence length A for individual filaments. In particular, have talked about actin filaments, intermediate filaments, and microtubules. Now, assuming we know the me- chanical properties of the individual filaments, what does that actually tell us about the assembly of filaments that we find in the cell? Or, to put it differently, if we knew elements of the cytoskeleton microtubules intermediate filaments actin filaments Figure 4.1: The cytoskeleton provides structural stability and is responsible for forces during cell loco- motion. Microtubules are thick hollow cylinders reaching out from the nucleus to the membrane, inter- mediate filaments can be found anywhere in the cytosol, and actin filaments are usually concentrated close to the cell membrane. the structural arrangement of filaments, could we then predict the stiffness of the over- all assembly? How does the filament microstructure affect cytoskeletal properties? Or, more precisely, how can we calculate the macroscopic network properties from the in- dividual microscopic filament properties? In mechanics, the derivation of macroscopic parameters based on microscopic considerations is referred to as homogenization. In this chapter, we illustrate the homogenization by means of three different examples, the fiber bundle model for filopodia, the network model for red blood cell membranes, and the tensegrity model for generic cell structures. 4.2 Fiber bundle model for filopodia Filopodia are thin dynamic cytoplasmic projections composed of tight bundles of long actin filaments extending from the leading edge of migrating cells.
    [Show full text]
  • Of Polarity Ups and Downs of Guided Vessel Sprouting
    Ups and Downs of Guided Vessel Sprouting: The Role of Polarity Christina Y. Lee and Victoria L. Bautch Physiology 26:326-333, 2011. doi:10.1152/physiol.00018.2011 You might find this additional info useful... This article cites 82 articles, 38 of which can be accessed free at: /content/26/5/326.full.html#ref-list-1 This article has been cited by 2 other HighWire hosted articles Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling Christopher W. Wilson, Leon H. Parker, Christopher J. Hall, Tanya Smyczek, Judy Mak, Ailey Crow, George Posthuma, Ann De Mazière, Meredith Sagolla, Cecile Chalouni, Philip Vitorino, Merone Roose-Girma, Søren Warming, Judith Klumperman, Philip S. Crosier and Weilan Ye Blood, November 21, 2013; 122 (22): 3678-3690. [Abstract] [Full Text] [PDF] Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton Michael S. Guerrero, J. Thomas Parsons and Amy H. Bouton Genes & Cancer, May , 2012; 3 (5-6): 371-381. [Abstract] [Full Text] [PDF] Downloaded from Updated information and services including high resolution figures, can be found at: /content/26/5/326.full.html Additional material and information about Physiology can be found at: http://www.the-aps.org/publications/physiol on August 25, 2014 This information is current as of August 25, 2014. Physiology (formerly published as News in Physiological Science) publishes brief review articles on major physiological developments. It is published bimonthly in February, April, June, August, October, and December by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2011 by the American Physiological Society.
    [Show full text]
  • Myth4-FERM Myosin Based Filopodia Initiation
    MyTH4-FERM Myosin based filopodia initiation A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Ashley L. Arthur IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Margaret A. Titus, PhD ADVISOR July 2020 © Ashley L Arthur 2020 ACKNOWLEDGEMENTS I would first and foremost like to advisor my mentor, Dr. Margaret Titus, for her unassailable commitment to training, enthusiasm for science and her sup- port of my career. Meg has been superb advisor, has made me a better scientist and communicator and I genuinely enjoyed working for her. I am grateful for the long list of positive experiences and opportunities I gained while working in the Titus lab. I would like to thank all of my past and present lab mates. Thank you to Hilary Bauer, Sinzi Cornea and Zoe Henrot for welcoming me into the lab when I started and especially to Karl Petersen who share his imaging and analysis ex- pertise. I am so grateful for the help and from my PLA project teammate Livia Songster, you brought such great energy to the project and to the lab. Thanks Casey Eddington, Annika Schroeder for their support, encouragement and help reading and discussing many aspect of this work. Thanks to the University of MN undergraduate students who joined my on research projects over the years espe- cially to Himanshu Jain. I would like to thank Jordan Beach at Loyola, Guillermo Marques, Mark Sanders, for their help with imaging. I thank Ashim Rai for his as- sistance with motor purification and motility assays.
    [Show full text]
  • Dynamics of Thin Filopodia During Sea Urchin Gastrulation
    Development 121, 2501-2511 (1995) 2501 Printed in Great Britain © The Company of Biologists Limited 1995 Dynamics of thin filopodia during sea urchin gastrulation Jeffrey Miller1, Scott E. Fraser2 and David McClay1,* 1Developmental, Cell and Molecular Biology, Duke University, SRC, Box 91000, Durham, NC 27708, USA 2Division of Biology, Beckman Institute (139-74), California Institute of Technology, Pasadena CA 91125, USA *Author for correspondence: e-mail [email protected] SUMMARY At gastrulation in the sea urchin embryo, a dramatic involvement in cell-cell interactions associated with rearrangement of cells establishes the three germ layers of signaling and patterning at gastrulation. Nickel-treatment, the organism. Experiments have revealed a number of cell which is known to create a patterning defect in skeleto- interactions at this stage that transfer patterning informa- genesis due to alterations in the ectoderm, alters the normal tion from cell to cell. Of particular significance, primary position-dependent differences in the thin filopodia. The mesenchyme cells, which are responsible for production of effect is present in recombinant embryos in which the the embryonic skeleton, have been shown to obtain ectoderm alone was treated with nickel, and is absent in extensive positional information from the embryonic recombinant embryos in which only the primary mes- ectoderm. In the present study, high resolution Nomarski enchyme cells were treated, suggesting that the filopodial imaging reveals the presence of very thin filopodia (0.2-0.4 length is substratum dependent rather than being primary µm in diameter) extending from primary mesenchyme cells mesenchyme cell autonomous. The thin filopodia provide a as well as from ectodermal and secondary mesenchyme means by which cells can contact others several cell cells.
    [Show full text]
  • 002 Sempozyum1 5 SON.Qxd
    Abstracts www.anatomy.org.tr doi:10.2399/ana.11.001s Abstracts for the Joint Meeting of Anatomical Societies, 19-22 May 2011, Bursa, Turkey Anatomy 2011; 5 Suppl: S1-S171, © 2011 TSACA Opening Lecture New genoarchitectonic viewpoints on the developing hypothalamus Puelles L effects suggests that, rather than being a diencephalic floor ele- ment, the hypothalamus is best understood as a transverse region Department of Human Anatomy, Faculty of lying ventral to the telencephalon and rostral to the dien- Medicine, University of Murcia, Murcia, Spain cephalon; the latter separates it from the midbrain. A number of gene expression patterns observed in the developing forebrain, part of the emergent genoarchitectonic neuroanatomy, have The anatomic concept of the hypothalamus changed consider- revealed the true topologic position of the hypothalamus, as well ably since its earliest definition. Tridimensional reconstructions, as the nature of its fundamental subdivisions. There are interest- experiments and many staining methods have expanded consid- ing parallelisms with genoarchitectonic patterns in the dien- erably the number of anatomical details recognized in this terri- cephalon and midbrain. In all these cases continuous longitudi- tory, probably one of the most complex in the brain. For a long nal domains can be distinguished, as well as a number of antero- time the predominant anatomic view has interpreted the hypo- posterior (transverse) neuromeric units of the neural wall. The thalamus as a longitudinal column at the floor of the dien- hypothalamus has been newly recognized to have two antero- cephalon, connected rostrally with the telencephalon and cau- posterior neuromeric subdivisions, named terminal and pedun- dally with the midbrain.
    [Show full text]
  • Functional Integrity of the Contractile Actin Cortex Is Safeguarded by Multiple Diaphanous-Related Formins
    Functional integrity of the contractile actin cortex is safeguarded by multiple Diaphanous-related formins Christof Litschkoa,1, Stefan Brühmanna,1, Agnes Csiszárb, Till Stephana, Vanessa Dimchevc,d, Julia Damiano-Guercioa, Alexander Junemanna, Sarah Körbera, Moritz Winterhoffa, Benjamin Nordholza,2, Nagendran Ramalingame, Michelle Peckhamf, Klemens Rottnerc,d, Rudolf Merkelb, and Jan Faixa,3 aInstitute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany; bInstitute of Complex Systems, ICS-7: Biomechanics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany; cDivision of Molecular Cell Biology, Zoological Institute, Technische Universität Braunschweig, 38106 Braunschweig, Germany; dMolecular Cell Biology Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; eAnn Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115; and fAstbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom Edited by Bruce L. Goode, Brandeis University, Waltham, MA, and accepted by Editorial Board Member Yale E. Goldman January 4, 2019 (received for review December 21, 2018) The contractile actin cortex is a thin layer of filamentous actin, This cortex contains actin, myosin, and associated factors assem- myosin motors, and regulatory proteins beneath the plasma bling into a multicomponent layer (9, 10), which is intimately linked to membrane crucial to cytokinesis, morphogenesis, and cell migra- the membrane in a phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]- tion. However, the factors regulating actin assembly in this dependent manner by the ezrin, radixin, and moesin (ERM) compartment are not well understood. Using the Dictyostelium family of proteins in animal cells (11, 12) and cortexillin (Ctx) in model system, we show that the three Diaphanous-related for- Dictyostelium (13–15).
    [Show full text]
  • Moesin, a New Cytoskeletal Protein and Constituent of Filopodia: Its Role in Cellular Functions
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 41 (1992), pp. 665—670 Moesin, a new cytoskeletal protein and constituent of filopodia: Its role in cellular functions HEINZ FURTHMAYR, WOLFGANG LANKES, and MANUEL AMIEVA Department of Pathology, Stanford University Medical Center, Stanford, California, USA Cell motility, cell attachment and cell-cell interaction arecrombie et al [8, 9], to the analysis of specialized cell attach- basic cellular processes that are of fundamental importancement sites with interference reflection microscopy [10], by during early development, injury and repair responses or in theimmunoelectron and light microscopy, of cell shape by scan- progression of tumors to metastatic disease. Cell movementsning electron microscopy [11, 12], it is clear that much has been often occur over large distances and the cells utilize trackslearned, but these complex processes are still not understood. (substrates) that are frequently modified, such as addition of galactose to laminin by cell surface galactosyl transferase [1] or Moesin is a member of a new family of cytoskeletal proteins proteolysis [2]. The invasion of developing tissues by other cell We have recently cloned and sequenced the complete cDNA types, for example, mesenchymal cells migrating into the ure-of a cellular protein with binding activity for heparin and teral bud [3], presumably involves an invasive phase thatheparan sulfate [13, 14]. We have termed this protein moesin includes: cell-matrix and cell-cell recognition phenomena, cell(membrane organizing extension spike protein, pronounced locomotion, and tissue degradation; a positioning phase of the[moe.ez.in]).
    [Show full text]
  • Modeling Membrane-Protein Interactions
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 4 September 2018 doi:10.20944/preprints201809.0055.v1 Peer-reviewed version available at Biomolecules 2018, 8, 120; doi:10.3390/biom8040120 Review Modeling membrane-protein interactions Haleh Alimohamadi and Padmini Rangamani* Department of Mechanical and Aerospace Engineering, University of California San Diego, CA 92093, USA * Correspondence: [email protected]; Tel.: +1-858-534-4734 Abstract: In order to alter and adjust the shape of the membrane, cells harness various mechanisms of curvature generation. Many of these curvature generation mechanisms rely on the interactions between peripheral membrane 1 proteins, integral membrane proteins, and lipids in the bilayer membrane. One of the challenges in modeling these 2 processes is identifying the suitable constitutive relationships that describe the membrane free energy that includes 3 protein distribution and curvature generation capability. Here, we review some of the commonly used continuum elastic 4 membrane models that have been developed for this purpose and discuss their applications. Finally, we address some 5 fundamental challenges that future theoretical methods need to overcome in order to push the boundaries of current model 6 applications. 7 8 Keywords: Plasma membrane; Spontaneous curvature; Helfrich energy; Area difference elastic model; Protein crowding; Deviatoric curvature 9 10 11 1. Introduction 12 The ability of cellular membranes to bend and adapt their configurations is critical for a variety of cellular functions 13 including membrane trafficking processes [1,2], fission [3,4], fusion [5,6], differentiation [7], cell motility [8,9], and signal 14 transduction [10–12]. In order to dynamically reshape the membrane, cells rely on a variety of molecular mechanisms from 15 forces exerted by the cytoskeleton [13–15] and membrane-protein interactions [16–19].
    [Show full text]
  • Universidad Nacional De Córdoba Facultad De Ciencias Médicas
    UNIVERSIDAD NACIONAL DE CÓRDOBA FACULTAD DE CIENCIAS MÉDICAS TRANSICIÓN EPITELIO-MESENQUIMÁTICA RENAL EN UN MODELO EXPERIMENTAL DE HIPERURICEMIA: PARTICIPACIÓN DE NALP-3 Y SUS FUNCIONES CANÓNICAS Y NO-CANÓNICAS Trabajo de Tesis para optar al Título de Doctor en Medicina y Cirugía Médico Cirujano Cesar Andrés Romero CÓRDOBA REPÚBLICA ARGENTINA 2014 1 COMISIÓN DE SEGUIMIENTO DE TESIS Director: Prof. Dr. Jorge H. Mukdsi Prof. Adjunto del Centro de Microscopía Electrónica. Facultad de Ciencias Médicas. Universidad Nacional de Córdoba. Integrantes: Prof. Dr. Luis I. Juncos Prof. Consulto de la Facultad de Ciencias Médicas. Universidad Nacional de Córdoba. Prof. Dr. Rodolfo E. Ávila Prof. Adjunto de la Cátedra de Biología Celular, Histología y Embriología. Facultad de Ciencia Médicas. Universidad Nacional de Córdoba. 2 Artículo 30º del Reglamento de la Carrera de Doctorado en Medicina y Cirugía “LA FACULTAD DE CIENCIAS MÉDICAS NO SE HACE SOLIDARIA CON LAS OPINIONES DE ESTA TESIS” 3 El presente trabajo de investigación se ha realizado en el Centro Microscopía Electrónica de la Facultad de Ciencias Médicas de la Universidad Nacional de Córdoba, de acuerdo con la reglamentación vigente en la Facultad de Ciencias Médicas de la Universidad Nacional de Córdoba para optar al título de Doctor en Medicina y Cirugía. Durante la ejecución, el autor fue Profesor Asistente del Centro de Microscopía Electrónica y contó con el apoyo financiero de subsidios del SECyT, CONICET, y FONCYT, otorgados al Centro de Microscopía Electrónica. 4 A mi esposa e hijas. A mis padres. A mis maestros. 5 AGRADECIMIENTOS Quiero expresar mis agradecimientos a la Prof. Dra. Alicia Inés Torres, Directora del Centro de Microscopía Electrónica por darme la posibilidad de realizar mi tesis doctoral y por brindarne su apoyo y consejo en todo momento.
    [Show full text]
  • Citocinas Proinflamatorias: Participación En La Modulación De La Actividad Del Melanoma Experimental B16
    eman ta zabal zazu Universidad Euskal Herriko del País Vasco Unibertsitatea MEDIKUNTZA ETA ODONTOLOGIA FAKULTATEA FACULTAD DE MEDICINA Y ODONTOLOGIA Dpto. de Biología Zelulen Biologia Celular e Histología eta Histologia Saila CITOCINAS PROINFLAMATORIAS: PARTICIPACIÓN EN LA MODULACIÓN DE LA ACTIVIDAD DEL MELANOMA EXPERIMENTAL B16 Por: Juan Carlos de la Cruz Conde Licenciado en Ciencias Biológicas LEIOA, 2014 Mi más sincero agradecimiento, A la Dra. Alicia García de Galdeano, directora de este trabajo por su sinceridad, apoyo, orientación, dedicación y estímulo permanente; pero sobre todo, por la confianza que depositó en mí para la realización del mismo. La aventura que iniciamos está a punto de terminar. Juntos recorrimos todo este camino y a pesar de las adversidades, ha merecido con mucho la pena aprender y trabajar colaborando contigo en este grupo. A los Profesores Mª Luz Cañavate, Juan Aréchaga, Mª Dolores Boyano, Antonia Álvarez, Francisco José Sáez, Fernando Unda, Enrique Hilario, Gorka Pérez-Yarza, Jon Arlucea, Carmen de la Hoz y Noelia Andollo, por todas las facilidades recibidas a lo largo de la realización de esta Tesis. Entre otras: la cesión de locales y el uso de equipos técnicos (citometría de flujo y microscopía de fluorescencia) e informáticos. Por su asesoramiento científico y haber puesto a mi disposición bibliografía. Así como, material de laboratorio de todo tipo, tanto fungible como diversos productos. Además, quiero hacer mención especial al Dr. Manuel García Sanz, que aunque ya no este físicamente, nos brindó su colaboración desinteresada y del que siempre obtuvimos todo tipo de facilidades y atenciones. A mis Amigos que forman parte del Departamento de Biología Celular e Histología, en especial a Loli García Vázquez, la persona que me enseñó con cariño y paciencia infinita.
    [Show full text]
  • The Co-Workers of Actin Filaments: from Cell Structures to Signals
    FOCUS ON CYTOSKELETAL DYNAMICS THE CO-WORKERS OF ACTIN FILAMENTS: FROM CELL STRUCTURES TO SIGNALS Céline Revenu, Rafika Athman, Sylvie Robine and Daniel Louvard Cells have various surface architectures, which allow them to carry out different specialized functions. Actin microfilaments that are associated with the plasma membrane are important for generating these cell-surface specializations, and also provide the driving force for remodelling cell morphology and triggering new cell behaviour when the environment is modified. This phenomenon is achieved through a tight coupling between cell structure and signal transduction, a process that is modulated by the regulation of actin-binding proteins. PHAGOCYTOSIS The integrity of the actin cytoskeleton is essential for cells networks that support cellular specializations, and then An actin-dependent process by to form and maintain their shape and structure. The focus on the ABPs that are implicated in these networks, which cells engulf external remodelling of the cytoskeleton in dynamic cellular illustrating their roles and regulation both in actin orga- particulate material by extension processes produces changes in cell shape and motility in nization and in the integration of signals that lead to and fusion of pseudopods. response to external stimuli, and is therefore involved actin dynamics (BOX 1). MICROVILLI in signal transduction. These features of the actin Small, finger-like projections cytoskeleton are regulated by a cohort of actin-binding Surface specializations and underlying networks (1–2 µm long and 100 nm wide) proteins (ABPs), which were initially considered to be Differentiated cells have morphological features that cor- that occur on the exposed structural components that organize a stable actin relate with their specialized functions in the organs and surfaces of epithelial cells to maximize the surface area.
    [Show full text]
  • Fascin in Cell Migration: More Than an Actin Bundling Protein
    biology Review Fascin in Cell Migration: More Than an Actin Bundling Protein Maureen C. Lamb and Tina L. Tootle * Anatomy and Cell Biology Department, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; [email protected] * Correspondence: [email protected] Received: 23 October 2020; Accepted: 13 November 2020; Published: 17 November 2020 Simple Summary: Cell migration is an essential biological process that regulates both development and diseases, such as cancer metastasis. Therefore, understanding the factors that promote cell migration is crucial. One of the factors known to regulate cell migration is the actin-binding protein, Fascin. Fascin is typically thought to promote cell migration through bundling actin to form migratory structures such as filopodia and invadapodia. However, Fascin has many other functions in the cell that may contribute to cell migration. How these novel functions promote cell migration and are regulated is still not well understood. Here, we review the structure of Fascin, the many functions of Fascin and how they may promote cell migration, how Fascin is regulated, and Fascin’s role in diseases such as cancer metastasis. Abstract: Fascin, an actin-binding protein, regulates many developmental migrations and contributes to cancer metastasis. Specifically, Fascin promotes cell motility, invasion, and adhesion by forming filopodia and invadopodia through its canonical actin bundling function. In addition to bundling actin, Fascin has non-canonical roles in the cell that are thought to promote cell migration. These non-canonical functions include regulating the activity of other actin-binding proteins, binding to and regulating microtubules, mediating mechanotransduction to the nucleus via interaction with the Linker of the Nucleoskeleton and Cytoskeleton (LINC) Complex, and localizing to the nucleus to regulate nuclear actin, the nucleolus, and chromatin modifications.
    [Show full text]