DOCSLIB.ORG

The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2020-01-15 The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila Hsi-Ju Chen University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Cell Biology Commons, and the Genetics Commons Repository Citation Chen H. (2020). The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila. GSBS Dissertations and Theses. https://doi.org/10.13028/ 0r15-ze63. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/1059 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila A Dissertation Presented by Hsi-Ju Chen Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester In partial fulfilment of the requirement for the requirements for the Degree of Doctor of Philosophy November 19, 2019 TABLE OF CONTENTS ABSTRACT CHAPTER I...................................................................................................... i INTRODUCTION................................................................................................. 1 The importance to maintain the health of the digestive tract............................... 1 The Hippo pathway.............................................................................................. 4 1. The core kinase of the Hippo signaling pathway and its conservation......................... 4 Drosophila ..................................................................................................... 4 Mammalian..................................................................................................... 10 2. Versatile upstream signals to regulate the Hippo signaling pathway............................ 15 Cell polarity.................................................................................................... 15 Cell-cell contact: cytoskeleton and mechanotransduction........................................ 22 Metabolite....................................................................................................... 24 Soluble factors................................................................................................. 25 (3) Crosstalk with other signaling to regulate ISCs behavior.......................................... 26 Mammalian intestine........................................................................................ 26 Drosophila midgut........................................................................................... 30 The Cell Junctions................................................................................................ 35 (1) The constituents of Vertebrates epithelial cell junctions........................................... 35 Tight junction................................................................................................... 35 Adherens junction............................................................................................. 41 Desmosome..................................................................................................... 42 (2) The cell junctions of the invertebrates exhibit comparable functions........................... 49 (3) The mechanisms that cell junctions adopt to regulate cell growth............................... 53 CHAPTER II..................................................................................................... ii ABSTRACT......................................................................................................... 57 INTRODUCTION............................................................................................... 58 RESULTS............................................................................................................. 61 Loss of smooth septate junction proteins in EBs leads to ISC proliferation..................... 61 Yorkie and Upd3 mediate the growth after loss of Ssk or Mesh.................................... 72 Ssk and Mesh expression and function are initiated in EBs to produce Upd3 for ISC proliferation..........................................................................................................78 Ssk and Mesh also have functions in ECs to regulate Yorkie-Upd3 and thereby ISC proliferation......................................................................................................... 90 The Ssk-Mesh complex are required for the co-localization with other junction proteins in ECs.....................................................................................................................98 Loss of Ssk and Mesh in EBs and ECs lead to different degrees of gut leakiness and animal viability..............................................................................................................105 Ssk and Mesh form a complex with and restrict the activity of Yki..............................109 DISCUSSION......................................................................................................115 MATERIALS AND METHODS ........................................................................118 TABLE 1.............................................................................................................124 ACKNOWLEDGMETNS.................................................................................. 130 CHAPTER III.................................................................................................135 DISCUSSION.....................................................................................................131 What lies between the smooth septate junctions and Yki?...........................................131 Not just glue, the smooth septate junctions serve as a signaling transduction center...........133 Two are not enough. Bicellular and tricellular junctions cooperatively strength the structure and integrity of the epithelia...................................................................................135 The roles of septate/tight junction protein in ISC proliferation and tissue homeostasis....137 Ssk and Mesh exhibit conserved functions in the insecta, but their vertebrate counterparts are multifaceted...................................................................................................141 Future direction & prospective application...............................................................143 REFERENCE................................................................................................ 148 FIGURE LIST Figure A. The activation mechanisms in the Hippo kinase cascade.....................9 Figure B. Multiple signals are integrated to regulate the Hippo pathway.............9 Figure C. The Hippo pathway coordinates multiple signals to regulate the activity of YAP/TAZ .........................................................................................................14 Figure D. The components of cell junctions are conserved..................................21 Figure E. The structure and the cell lineages of the mammalian intestine.......................27 Figure F. The Drosophila midgut..........................................................................31 Figure G. Epithelial niche and conserved signaling regulate ISC division and cell fate to control homeostasis....................................................................................................32 Figure H. Schematic representation of the basic structural components of tight junctions and adherens junctions...........................................................................40 Figure I. Schematic representation of the structural components of Desmosome........43 Figure J. Proposed models........................................................................................147 Figure 1. Loss of smooth septate junction proteins in EBs leads to ISC proliferation...............62 Figure 2. Ssk and mesh loss of function mutant clones increase proliferation majorly through an ISC-non-autonomous mechanism.................................................................................66 Figure 3. Ssk and mesh mutant neither skew the asymmetric division nor affect the differentiation of ISCs................................................................................................70 Figure 4. Upd3 is secreted out to mediate the growth after loss of Ssk or Mesh......................73 Figure 5. Yki regulates the Upd3 expression to control the growth after loss of Ssk or Mesh....76 Figure 6. Ssk and Mesh expression and function are initiated in EBs.................................80 Figure 7. Loss of Ssk or Mesh within EBs does not affect the differentiation into ECs.........85 Figure 8. Loss of Ssk or Mesh within ISCs did not show an increased proliferation phenotype.................................................................................................................86 Figure 9. Loss of Ssk or Mesh function initiates the expression of Upd3 within EBs............87 Figure 10. Ssk and Mesh also have
Load more

Recommended publications
  • Keratins and Plakin Family Cytolinker Proteins Control the Length Of
    RESEARCH ARTICLE Keratins and plakin family cytolinker proteins control the length of epithelial microridge protrusions Yasuko Inaba*, Vasudha Chauhan, Aaron Paul van Loon, Lamia Saiyara Choudhury, Alvaro Sagasti* Molecular, Cell and Developmental Biology Department and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States Abstract Actin filaments and microtubules create diverse cellular protrusions, but intermediate filaments, the strongest and most stable cytoskeletal elements, are not known to directly participate in the formation of protrusions. Here we show that keratin intermediate filaments directly regulate the morphogenesis of microridges, elongated protrusions arranged in elaborate maze-like patterns on the surface of mucosal epithelial cells. We found that microridges on zebrafish skin cells contained both actin and keratin filaments. Keratin filaments stabilized microridges, and overexpressing keratins lengthened them. Envoplakin and periplakin, plakin family cytolinkers that bind F-actin and keratins, localized to microridges, and were required for their morphogenesis. Strikingly, plakin protein levels directly dictate microridge length. An actin-binding domain of periplakin was required to initiate microridge morphogenesis, whereas periplakin-keratin binding was required to elongate microridges. These findings separate microridge morphogenesis into distinct steps, expand our understanding of intermediate filament functions, and identify microridges as protrusions that integrate actin and intermediate filaments. *For correspondence: [email protected] (YI); Introduction [email protected] (AS) Cytoskeletal filaments are scaffolds for membrane protrusions that create a vast diversity of cell shapes. The three major classes of cytoskeletal elements—microtubules, actin filaments, and inter- Competing interests: The mediate filaments (IFs)—each have distinct mechanical and biochemical properties and associate authors declare that no with different regulatory proteins, suiting them to different functions.
    [Show full text]
  • Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer
    cancers Review Myosin Motors: Novel Regulators and Therapeutic Targets in Colorectal Cancer Nayden G. Naydenov 1, Susana Lechuga 1, Emina H. Huang 2 and Andrei I. Ivanov 1,* 1 Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; [email protected] (N.G.N.); [email protected] (S.L.) 2 Departments of Cancer Biology and Colorectal Surgery, Cleveland Clinic Foundation, Cleveland, OH 44195, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-216-445-5620 Simple Summary: Colorectal cancer (CRC) is a deadly disease that may go undiagnosed until it presents at an advanced metastatic stage for which few interventions are available. The develop- ment and metastatic spread of CRC is driven by remodeling of the actin cytoskeleton in cancer cells. Myosins represent a large family of actin motor proteins that play key roles in regulating actin cytoskeleton architecture and dynamics. Different myosins can move and cross-link actin filaments, attach them to the membrane organelles and translocate vesicles along the actin filaments. These diverse activities determine the key roles of myosins in regulating cell proliferation, differ- entiation and motility. Either mutations or the altered expression of different myosins have been well-documented in CRC; however, the roles of these actin motors in colon cancer development remain poorly understood. The present review aims at summarizing the evidence that implicate myosin motors in regulating CRC growth and metastasis and discusses the mechanisms underlying the oncogenic and tumor-suppressing activities of myosins. Abstract: Colorectal cancer (CRC) remains the third most common cause of cancer and the second most common cause of cancer deaths worldwide.
    [Show full text]
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
    [Show full text]
  • Microrna Regulatory Pathways in the Control of the Actin–Myosin Cytoskeleton
    cells Review MicroRNA Regulatory Pathways in the Control of the Actin–Myosin Cytoskeleton , , Karen Uray * y , Evelin Major and Beata Lontay * y Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; [email protected] * Correspondence: [email protected] (K.U.); [email protected] (B.L.); Tel.: +36-52-412345 (K.U. & B.L.) The authors contributed equally to the manuscript. y Received: 11 June 2020; Accepted: 7 July 2020; Published: 9 July 2020 Abstract: MicroRNAs (miRNAs) are key modulators of post-transcriptional gene regulation in a plethora of processes, including actin–myosin cytoskeleton dynamics. Recent evidence points to the widespread effects of miRNAs on actin–myosin cytoskeleton dynamics, either directly on the expression of actin and myosin genes or indirectly on the diverse signaling cascades modulating cytoskeletal arrangement. Furthermore, studies from various human models indicate that miRNAs contribute to the development of various human disorders. The potentially huge impact of miRNA-based mechanisms on cytoskeletal elements is just starting to be recognized. In this review, we summarize recent knowledge about the importance of microRNA modulation of the actin–myosin cytoskeleton affecting physiological processes, including cardiovascular function, hematopoiesis, podocyte physiology, and osteogenesis. Keywords: miRNA; actin; myosin; actin–myosin complex; Rho kinase; cancer; smooth muscle; hematopoiesis; stress fiber; gene expression; cardiovascular system; striated muscle; muscle cell differentiation; therapy 1. Introduction Actin–myosin interactions are the primary source of force generation in mammalian cells. Actin forms a cytoskeletal network and the myosin motor proteins pull actin filaments to produce contractile force. All eukaryotic cells contain an actin–myosin network inferring contractile properties to these cells.
    [Show full text]
  • An Uncommon Clinical Presentation of Relapsing Dilated Cardiomyopathy with Identification of Sequence Variations in MYNPC3, KCNH2 and Mitochondrial Trna Cysteine M
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by George Washington University: Health Sciences Research Commons (HSRC) Himmelfarb Health Sciences Library, The George Washington University Health Sciences Research Commons Pediatrics Faculty Publications Pediatrics 6-2015 An uncommon clinical presentation of relapsing dilated cardiomyopathy with identification of sequence variations in MYNPC3, KCNH2 and mitochondrial tRNA cysteine M. J. Guillen Sacoto Kimberly A. Chapman George Washington University D. Heath M. B. Seprish Dina Zand George Washington University Follow this and additional works at: http://hsrc.himmelfarb.gwu.edu/smhs_peds_facpubs Part of the Pediatrics Commons Recommended Citation Guillen Sacoto, M.J., Chapman, K.A., Heath, D., Seprish, M.B., Zand, D.J. (2015). An uncommon clinical presentation of relapsing dilated cardiomyopathy with identification of sequence variations in MYNPC3, KCNH2 and mitochondrial tRNA cysteine. Molecular Genetics and Metabolism Reports, 3, 47-54. doi:10.1016/j.ymgmr.2015.03.007 This Journal Article is brought to you for free and open access by the Pediatrics at Health Sciences Research Commons. It has been accepted for inclusion in Pediatrics Faculty Publications by an authorized administrator of Health Sciences Research Commons. For more information, please contact [email protected]. Molecular Genetics and Metabolism Reports 3 (2015) 47–54 Contents lists available at ScienceDirect Molecular Genetics and Metabolism Reports journal homepage: http://www.journals.elsevier.com/molecular-genetics-and- metabolism-reports/ Case Report An uncommon clinical presentation of relapsing dilated cardiomyopathy with identification of sequence variations in MYNPC3, KCNH2 and mitochondrial tRNA cysteine Maria J. Guillen Sacoto a,1, Kimberly A.
    [Show full text]
  • Novel Myosin Mutations for Hereditary Hearing Loss Revealed by Targeted Genomic Capture and Massively Parallel Sequencing
    European Journal of Human Genetics (2014) 22, 768–775 & 2014 Macmillan Publishers Limited All rights reserved 1018-4813/14 www.nature.com/ejhg ARTICLE Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing Zippora Brownstein1,6, Amal Abu-Rayyan2,6, Daphne Karfunkel-Doron1, Serena Sirigu3, Bella Davidov4, Mordechai Shohat1,4, Moshe Frydman1,5, Anne Houdusse3, Moien Kanaan2 and Karen B Avraham*,1 Hereditary hearing loss is genetically heterogeneous, with a large number of genes and mutations contributing to this sensory, often monogenic, disease. This number, as well as large size, precludes comprehensive genetic diagnosis of all known deafness genes. A combination of targeted genomic capture and massively parallel sequencing (MPS), also referred to as next-generation sequencing, was applied to determine the deafness-causing genes in hearing-impaired individuals from Israeli Jewish and Palestinian Arab families. Among the mutations detected, we identified nine novel mutations in the genes encoding myosin VI, myosin VIIA and myosin XVA, doubling the number of myosin mutations in the Middle East. Myosin VI mutations were identified in this population for the first time. Modeling of the mutations provided predicted mechanisms for the damage they inflict in the molecular motors, leading to impaired function and thus deafness. The myosin mutations span all regions of these molecular motors, leading to a wide range of hearing phenotypes, reinforcing the key role of this family of proteins in auditory function. This study demonstrates that multiple mutations responsible for hearing loss can be identified in a relatively straightforward manner by targeted-gene MPS technology and concludes that this is the optimal genetic diagnostic approach for identification of mutations responsible for hearing loss.
    [Show full text]
  • Dietary Genistein Supplementation for Breeders and Their Offspring
    www.nature.com/scientificreports OPEN Dietary genistein supplementation for breeders and their ofspring improves the growth performance Received: 29 November 2017 Accepted: 13 March 2018 and immune function of broilers Published: xx xx xxxx Zengpeng Lv, Hao Fan, Beibei Zhang, Kun Xing & Yuming Guo Genistein (GEN) is mainly extracted from soy plants and has potential functions as an antioxidant and in promoting immune function and growth. This study evaluated the efects of feeding breeders and their ofspring dietary GEN on the immune function and growth performance of broiler chicks. Breeders were assigned to a control diet or GEN diet (control diet +400 mg/kg GEN), and their ofspring were fed a control diet or GEN diet (control diet +40 mg/kg GEN). GEN treatment increased the body weight gain, tibial length, tibial width and slaughter performance of broilers and decreased the feed conversion ratio. The treatment also afected skeletal muscle myosin assembly and growth and increased growth hormone levels and IGF-I and IGFBP1 expression. Following GEN treatment, antigen processing and presentation, macrophage activation, B lymphocyte, NK cell and helper T cell proliferation, and CD4+ T lymphocyte diferentiation all increased signifcantly. Increases were also observed in IgM and IgG concentrations, antibody titers, and antioxidant capacity. In addition, GEN treatment activated the Toll-like receptor signaling pathway and MAPK cascade signaling pathway. In summary, dietary GEN supplementation for breeders and their ofspring can improve the growth performance and immune function of broiler chicks. Isofavones (ISFs), including genistein (GEN), daidzein and glycitein, are widely found in soy plants and have potential functions as antioxidants and in immune function and detoxifcation1.
    [Show full text]
  • Rna-Sequencing Applications: Gene Expression Quantification and Methylator Phenotype Identification
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2013 RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION Guoshuai Cai Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Bioinformatics Commons, Computational Biology Commons, and the Medicine and Health Sciences Commons Recommended Citation Cai, Guoshuai, "RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION" (2013). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 386. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/386 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. RNA-SEQUENCING APPLICATIONS: GENE EXPRESSION QUANTIFICATION AND METHYLATOR PHENOTYPE IDENTIFICATION
    [Show full text]
  • SARS-Cov-2 Infection of Human Ipsc-Derived Cardiac Cells Predicts Novel Cytopathic Features in Hearts of COVID-19 Patients
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.25.265561; this version posted September 12, 2020. 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-ND 4.0 International license. SARS-CoV-2 infection of human iPSC-derived cardiac cells predicts novel cytopathic features in hearts of COVID-19 patients Juan A. Pérez-Bermejo*1, Serah Kang*1, Sarah J. Rockwood*1, Camille R. Simoneau*1,2, David A. Joy1,3, Gokul N. Ramadoss1,2, Ana C. Silva1, Will R. Flanigan1,3, Huihui Li1, Ken Nakamura1,4, Jeffrey D. Whitman5, Melanie Ott†,1, Bruce R. Conklin†,1,6,7,8, Todd C. McDevitt†1,9 * These authors contributed equally to this work. † Co-corresponding authors. 1 Gladstone Institutes, San Francisco, CA 2 Biomedical Sciences PhD Program, University of California, San Francisco, CA 3 UC Berkeley UCSF Joint Program in Bioengineering, Berkeley, CA 4 UCSF Department of Neurology, San Francisco, CA 5 UCSF Department of Laboratory Medicine, San Francisco, CA 6 Innovative Genomics Institute, Berkeley, CA 7 UCSF Department of Ophthalmology, San Francisco, CA 8 UCSF Department of Medicine, San Francisco, CA 9 UCSF Department of Bioengineering and Therapeutic Sciences, San Francisco, CA ABSTRACT Although COVID-19 causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human iPSC-derived heart cells to SARS-CoV-2 revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes.
    [Show full text]
  • (MYO7A) Auditory Mutation V a Street, J C Kallman, K L Kiemele
    1of8 ELECTRONIC LETTER J Med Genet: first published as 10.1136/jmg.2003.013557 on 30 April 2004. Downloaded from Modifier controls severity of a novel dominant low- frequency MyosinVIIA (MYO7A) auditory mutation V A Street, J C Kallman, K L Kiemele ............................................................................................................................... J Med Genet 2004;41:e62 (http://www.jmedgenet.com/cgi/content/full/41/5/e62). doi: 10.1136/jmg.2003.013557 earing impairment is a common sensory deficit with both genetic and environmental aetiologies. Pre-lingual Key points Hhearing loss affects approximately 1 in every 1000 children in the United States with a genetic basis in about N Mutations within myosin molecules can lead to 50% of the cases.1 An additional 1 per 1000 individuals syndromic and non-syndromic hearing impairment. 1 experience auditory deficits prior to adulthood. Large N We describe the genetic mapping of progressive pedigrees with monogenic non-syndromic hearing impair- sensorineural hearing loss first affecting low-frequency ment have allowed genetic mapping of at least 80 chromo- auditory thresholds within a large human pedigree to somal locations harbouring auditory-related deafness (DFN) chromosome 11q13.5. A maximal pairwise LOD score loci with the identification of over 30 DFN genes.2 The DFN of 7.23 was obtained with marker D11S4207. inheritance pattern is designated by A dominant, B recessive, and M modifier, with a number following A, B,orM N WeidentifiedamyosinVIIA(MYO7A) G2164C indicating the relative order in which the locus was mutation that co-segregates with auditory dysfunction identified. For example, DFNA1 represents the first dom- in the pedigree. The mutation results in a predicted inantly inherited deafness locus mapped in humans.
    [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]
  • An Unconventional Role for the Septate Junctions and Gliotactin in Cell Division
    AN UNCONVENTIONAL ROLE FOR THE SEPTATE JUNCTIONS AND GLIOTACTIN IN CELL DIVISION by KRISTI CHARISH B.Sc. (Molecular Biology and Biochemistry), Simon Fraser University, 2004 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Zoology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) July 2011 © Kristi Charish, 2011 Abstract The focus of this thesis is to investigate the integration of cell division with the septate junction domain in the Drosophila imaginal wing disc epithelium. Columnar epithelia of the imaginal wing disc exhibit complex architecture due to an elaborate series of junctions that are found throughout the membrane. During cell division, these junctions are maintained while new junctions are established; however, their role and influence during mitosis is unclear. This thesis shows that the septate junctions are essential for cytokinesis and Gliotactin at the tricellular junctions is necessary to localize cell division to the septate junction domain, and illustrates a unique role for Gliotactin and the septate junctions outside their classic role of maintaining a permeability barrier. The septate junctions are basolaterally localized transmembrane junctions required in epithelial cells to form a permeability barrier. Although the septate junctions are formed by a large protein complex, this thesis only investigates the three core SJ proteins, NeurexinIV (NrxIV), Coracle (Cor), and Neuroglian (Nrg). Gliotactin (Gli), a Drosophila Neuroligin homologue, is a septate junction associated protein concentrated at the tricellular junction (TCJ), which is necessary to maintain the septate junction permeability barrier. Loss of any of the septate junction proteins, or Gliotactin, leads to structural disruption of the septate junctions and loss of the permeability barrier in a wide range of epithelial derived tissues.
    [Show full text]