Bending of the ''9+2'' Axoneme Analysed by the Finite Element Method
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Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct
cells Article Sorting Nexin 27 Regulates the Lysosomal Degradation of Aquaporin-2 Protein in the Kidney Collecting Duct Hyo-Jung Choi 1,2, Hyo-Ju Jang 1,3, Euijung Park 1,3, Stine Julie Tingskov 4, Rikke Nørregaard 4, Hyun Jun Jung 5 and Tae-Hwan Kwon 1,3,* 1 Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, Korea; [email protected] (H.-J.C.); [email protected] (H.-J.J.); [email protected] (E.P.) 2 New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Taegu 41061, Korea 3 BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science, School of Medicine, Kyungpook National University, Taegu 41944, Korea 4 Department of Clinical Medicine, Aarhus University, Aarhus 8200, Denmark; [email protected] (S.J.T.); [email protected] (R.N.) 5 Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; [email protected] * Correspondence: [email protected]; Tel.: +82-53-420-4825; Fax: +82-53-422-1466 Received: 30 March 2020; Accepted: 11 May 2020; Published: 13 May 2020 Abstract: Sorting nexin 27 (SNX27), a PDZ (Postsynaptic density-95/Discs large/Zonula occludens 1) domain-containing protein, cooperates with a retromer complex, which regulates intracellular trafficking and the abundance of membrane proteins. Since the carboxyl terminus of aquaporin-2 (AQP2c) has a class I PDZ-interacting motif (X-T/S-X-F), the role of SNX27 in the regulation of AQP2 was studied. Co-immunoprecipitation assay of the rat kidney demonstrated an interaction of SNX27 with AQP2. -
The Cytoskeleton of Giardia Lamblia
International Journal for Parasitology 33 (2003) 3–28 www.parasitology-online.com Invited review The cytoskeleton of Giardia lamblia Heidi G. Elmendorfa,*, Scott C. Dawsonb, J. Michael McCafferyc aDepartment of Biology, Georgetown University, 348 Reiss Building 37th and O Sts. NW, Washington, DC 20057, USA bDepartment of Molecular and Cell Biology, University of California Berkeley, 345 LSA Building, Berkeley, CA 94720, USA cDepartment of Biology, Johns Hopkins University, Integrated Imaging Center, Baltimore, MD 21218, USA Received 18 July 2002; received in revised form 18 September 2002; accepted 19 September 2002 Abstract Giardia lamblia is a ubiquitous intestinal pathogen of mammals. Evolutionary studies have also defined it as a member of one of the earliest diverging eukaryotic lineages that we are able to cultivate and study in the laboratory. Despite early recognition of its striking structure resembling a half pear endowed with eight flagella and a unique ventral disk, a molecular understanding of the cytoskeleton of Giardia has been slow to emerge. Perhaps most importantly, although the association of Giardia with diarrhoeal disease has been known for several hundred years, little is known of the mechanism by which Giardia exacts such a toll on its host. What is clear, however, is that the flagella and disk are essential for parasite motility and attachment to host intestinal epithelial cells. Because peristaltic flow expels intestinal contents, attachment is necessary for parasites to remain in the small intestine and cause diarrhoea, underscoring the essential role of the cytoskeleton in virulence. This review presents current day knowledge of the cytoskeleton, focusing on its role in motility and attachment. -
Molecular Evolutionary Analysis of Plastid Genomes in Nonphotosynthetic Angiosperms and Cancer Cell Lines
The Pennsylvania State University The Graduate School Department or Biology MOLECULAR EVOLUTIONARY ANALYSIS OF PLASTID GENOMES IN NONPHOTOSYNTHETIC ANGIOSPERMS AND CANCER CELL LINES A Dissertation in Biology by Yan Zhang 2012 Yan Zhang Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Dec 2012 The Dissertation of Yan Zhang was reviewed and approved* by the following: Schaeffer, Stephen W. Professor of Biology Chair of Committee Ma, Hong Professor of Biology Altman, Naomi Professor of Statistics dePamphilis, Claude W Professor of Biology Dissertation Adviser Douglas Cavener Professor of Biology Head of Department of Biology *Signatures are on file in the Graduate School iii ABSTRACT This thesis explores the application of evolutionary theory and methods in understanding the plastid genome of nonphotosynthetic parasitic plants and role of mutations in tumor proliferations. We explore plastid genome evolution in parasitic angiosperms lineages that have given up the primary function of plastid genome – photosynthesis. Genome structure, gene contents, and evolutionary dynamics were analyzed and compared in both independent and related parasitic plant lineages. Our studies revealed striking similarities in changes of gene content and evolutionary dynamics with the loss of photosynthetic ability in independent nonphotosynthetic plant lineages. Evolutionary analysis suggests accelerated evolution in the plastid genome of the nonphotosynthetic plants. This thesis also explores the application of phylogenetic and evolutionary analysis in cancer biology. Although cancer has often been likened to Darwinian process, very little application of molecular evolutionary analysis has been seen in cancer biology research. In our study, phylogenetic approaches were used to explore the relationship of several hundred established cancer cell lines based on multiple sequence alignments constructed with variant codons and residues across 494 and 523 genes. -
Cytoskeleton Cytoskeleton
CYTOSKELETON CYTOSKELETON The cytoskeleton is composed of three principal types of protein filaments: actin filaments, intermediate filaments, and microtubules, which are held together and linked to subcellular organelles and the plasma membrane by a variety of accessory proteins Muscle Contraction • Skeletal muscles are bundles of muscle fibers • Most of the cytoplasm consists of myofibrils, which are cylindrical bundles of two types of filaments: thick filaments of myosin (about 15 run in diameter) and thin filaments of actin (about 7 nm in diameter). • Each myofibril is organized as a chain of contractile units called sarcomeres, which are responsible for the striated appearance of skeletal and cardiac muscle. Structure of muscle cells Sarcomere • The ends of each sarcomere are defined by the Z disc. • Within each sarcomere, dark bands (called A bands because they are anisotropic when viewed with polarized light) alternate with light bands (called I bands for isotropic). • The I bands contain only thin (actin) filaments, whereas the A bands contain thick (myosin) filaments. • The myosin and actin filaments overlap in peripheral regions of the A band, whereas a middle region (called the H zone) contains only myosin. Muscle contraction • The basis for understanding muscle contraction is the sliding filament model, first proposed in 1954 both by Andrew Huxley and Ralph Niedergerke and by Hugh Huxley and Jean Hanson • During muscle contraction each sarcomere shortens, bringing the Z discs closer together. • There is no change in the width of the A band, but both the I bands and the H zone almost completely disappear. • These changes are explained by the actin and myosin filaments sliding past one another so that the actin filaments move into the A band and H zone. -
Sorting Nexin-27 Regulates AMPA Receptor Trafficking Through The
RESEARCH ARTICLE Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2 Kirsty J McMillan1†*, Paul J Banks2†, Francesca LN Hellel1, Ruth E Carmichael1, Thomas Clairfeuille3, Ashley J Evans1, Kate J Heesom4, Philip Lewis4, Brett M Collins3, Zafar I Bashir2, Jeremy M Henley1, Kevin A Wilkinson1*, Peter J Cullen1* 1School of Biochemistry, University of Bristol, Bristol, United Kingdom; 2School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom; 3Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia; 4Proteomics facility, School of Biochemistry, University of Bristol, Bristol, United Kingdom Abstract The endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies, we performed proteomics in rat primary neurons to identify SNX27-dependent cargoes, and identified proteins linked to excitotoxicity, epilepsy, intellectual disabilities, and working memory deficits. Focusing on the *For correspondence: synaptic adhesion molecule LRFN2, we established that SNX27 binds to LRFN2 and regulates its [email protected] endosomal sorting. Furthermore, LRFN2 associates with AMPA receptors and knockdown of (KJMM); LRFN2 results in decreased surface AMPA receptor expression, reduced synaptic activity, and [email protected] attenuated hippocampal long-term potentiation. Overall, our study provides an additional (KAW); mechanism by which SNX27 can control AMPA receptor-mediated synaptic transmission and [email protected] (PJC) plasticity indirectly through the sorting of LRFN2 and offers molecular insight into the perturbed †These authors contributed function of SNX27 and LRFN2 in a range of neurological conditions. -
Cilia and Flagella: from Discovery to Disease Dylan J
Dartmouth Undergraduate Journal of Science Volume 20 Article 2 Number 1 Assembly 2017 Cilia and Flagella: From Discovery to Disease Dylan J. Cahill Dylan Cahill, [email protected] Follow this and additional works at: https://digitalcommons.dartmouth.edu/dujs Part of the Engineering Commons, Life Sciences Commons, Medicine and Health Sciences Commons, Physical Sciences and Mathematics Commons, and the Social and Behavioral Sciences Commons Recommended Citation Cahill, Dylan J. (2017) "Cilia and Flagella: From Discovery to Disease," Dartmouth Undergraduate Journal of Science: Vol. 20 : No. 1 , Article 2. Available at: https://digitalcommons.dartmouth.edu/dujs/vol20/iss1/2 This Research Article is brought to you for free and open access by the Student-led Journals and Magazines at Dartmouth Digital Commons. It has been accepted for inclusion in Dartmouth Undergraduate Journal of Science by an authorized editor of Dartmouth Digital Commons. For more information, please contact [email protected]. BIOLOGY Cilia and Flagella: FromCilia and Discovery Flagella: to Disease From Discovery to Disease BY DYLAN CAHILL ‘18 Introduction certain insect sperm fagella (3, 5, 6). A unique Figure 1: Chlamydomonas intracellular transport mechanism known as reinhardtii, a single-celled, bi- In 1674, peering through the lens of a crude flagellate green alga, viewed intrafagellar transport is responsible for the light microscope, Antoni van Leeuwenhoek with a scanning electron assembly and maintenance of these organelles Chlamydomonas observed individual living cells for the frst time microscope. is (3, 6). Cilia and fagella are primarily composed a model organism in flagellar in history (1). He noted long, thin appendages of the protein tubulin, which polymerizes into dynamics and motility studies. -
Ciliary Dyneins and Dynein Related Ciliopathies
cells Review Ciliary Dyneins and Dynein Related Ciliopathies Dinu Antony 1,2,3, Han G. Brunner 2,3 and Miriam Schmidts 1,2,3,* 1 Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg University Faculty of Medicine, Mathildenstrasse 1, 79106 Freiburg, Germany; [email protected] 2 Genome Research Division, Human Genetics Department, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 KL Nijmegen, The Netherlands; [email protected] 3 Radboud Institute for Molecular Life Sciences (RIMLS), Geert Grooteplein Zuid 10, 6525 KL Nijmegen, The Netherlands * Correspondence: [email protected]; Tel.: +49-761-44391; Fax: +49-761-44710 Abstract: Although ubiquitously present, the relevance of cilia for vertebrate development and health has long been underrated. However, the aberration or dysfunction of ciliary structures or components results in a large heterogeneous group of disorders in mammals, termed ciliopathies. The majority of human ciliopathy cases are caused by malfunction of the ciliary dynein motor activity, powering retrograde intraflagellar transport (enabled by the cytoplasmic dynein-2 complex) or axonemal movement (axonemal dynein complexes). Despite a partially shared evolutionary developmental path and shared ciliary localization, the cytoplasmic dynein-2 and axonemal dynein functions are markedly different: while cytoplasmic dynein-2 complex dysfunction results in an ultra-rare syndromal skeleto-renal phenotype with a high lethality, axonemal dynein dysfunction is associated with a motile cilia dysfunction disorder, primary ciliary dyskinesia (PCD) or Kartagener syndrome, causing recurrent airway infection, degenerative lung disease, laterality defects, and infertility. In this review, we provide an overview of ciliary dynein complex compositions, their functions, clinical disease hallmarks of ciliary dynein disorders, presumed underlying pathomechanisms, and novel Citation: Antony, D.; Brunner, H.G.; developments in the field. -
3D Structure of Eukaryotic Flagella in a Quiescent State Revealed by Cryo-Electron Tomography
3D structure of eukaryotic flagella in a quiescent state revealed by cryo-electron tomography Daniela Nicastro*†, J. Richard McIntosh‡§, and Wolfgang Baumeister* *Abteilung Molekulare Strukturbiologie, Max-Planck-Institut fu¨r Biochemie, 82152 Martinsried, Germany; and ‡Laboratory for 3D Electron Microscopy of Cells, Department of Molecular, Cellular, and Developmental Biology, UCB 347, University of Colorado, Boulder, CO 80309 Contributed by J. Richard McIntosh, September 21, 2005 We have used cryo-electron tomography to investigate the 3D position. McEwen et al. (12) have used electron tomography structure and macromolecular organization of intact, frozen- (ET) to study chemically fixed and resin-embedded cilia from hydrated sea urchin sperm flagella in a quiescent state. The newt lung. ET uses 2D projection images from many different tomographic reconstructions provide information at a resolution viewing angles to reconstruct an object in three dimensions (13, better than 6 nm about the in situ arrangements of macromolecules 14). These researchers were able to identify major features of that are key for flagellar motility. We have visualized the hep- axonemes in the tomographic reconstructions of the 250-nm- tameric rings of the motor domains in the outer dynein arm thick sections, but at a resolution of Ϸ12 nm, detailed insights complex and determined that they lie parallel to the plane that into the molecular organization of the axoneme were not contains the axes of neighboring flagellar microtubules. Both the available. material associated with the central pair of microtubules and the Thanks to technological advances of the past decade, ET can radial spokes display a plane of symmetry that helps to explain the now be applied to relatively large, frozen-hydrated structures. -
Cell Adhesion: a FERM Grasp of the Tail Sorts out Integrins
Current Biology Vol 22 No 17 R692 and how the cell integrates them with 5. Nott, A., Jung, H.S., Koussevitzky, S., and retrograde pathway that functions in drought Chory, J. (2006). Plastid-to-nucleus retrograde and high light signaling in Arabidopsis. Plant one another and other cell/organelle signaling. Annu. Rev. Plant Biol. 57, 739–759. Cell 23, 3992–4012. functions. Answering these questions 6. Koussevitzky, S., Nott, A., Mockler, T.C., 15. Grieshaber, N.A., Fischer, E.R., Mead, D.J., will likely be a challenge considering Hong, F., Sachetto-Martins, G., Surpin, M., Dooley, C.A., and Hackstadt, T. (2004). Lim, J., Mittler, R., and Chory, J. (2007). Chlamydial histone-DNA interactions are that many of the biosynthetic pathways Signals from chloroplasts converge to regulate disrupted by a metabolite in the involved are essential, which limits our nuclear gene expression. Science 316, methylerythritol phosphate pathway of 715–719. isoprenoid biosynthesis. Proc. Natl. Acad. Sci. ability to generate loss-of-function 7. Susek, R.E., Ausubel, F.M., and Chory, J. USA 101, 7451–7456. mutants. Furthermore, the essential (1993). Signal transduction mutants of 16. Grieshaber, N.A., Sager, J.B., Dooley, C.A., and integrated nature of the plastid Arabidopsis uncouple nuclear CAB and RBCS Hayes, S.F., and Hackstadt, T. (2006). gene expression from chloroplast Regulation of the Chlamydia trachomatis leads to pleiotropic affects when its development. Cell 74, 787–799. histone H1-like protein Hc2 is IspE dependent function is compromised, which can 8. Woodson, J.D., Perez-Ruiz, J.M., and Chory, J. and IhtA independent. -
RSPH6A Is Required for Sperm Flagellum Formation and Male
© 2018. Published by The Company of Biologists Ltd | Journal of Cell Science (2018) 131, jcs221648. doi:10.1242/jcs.221648 RESEARCH ARTICLE RSPH6A is required for sperm flagellum formation and male fertility in mice Ferheen Abbasi1,2,‡, Haruhiko Miyata1,‡, Keisuke Shimada1, Akane Morohoshi1,2, Kaori Nozawa1,2,*, Takafumi Matsumura1,3, Zoulan Xu1,3, Putri Pratiwi1 and Masahito Ikawa1,2,3,4,§ ABSTRACT (Carvalho-Santos et al., 2011) and is used for sensing and The flagellum is an evolutionarily conserved appendage used for locomotion. Mammalian spermatozoan flagella are highly sensing and locomotion. Its backbone is the axoneme and a specialized to carry male genetic material into the female component of the axoneme is the radial spoke (RS), a protein reproductive tract and fertilize the oocyte. Internal cross-sections ‘ ’ complex implicated in flagellar motility regulation. Numerous diseases show that the flagellum comprises a 9+2 microtubule structure: a occur if the axoneme is improperly formed, such as primary ciliary bundle of nine microtubule doublets that surround a central pair of dyskinesia (PCD) and infertility. Radial spoke head 6 homolog A single microtubules (Satir and Christensen, 2007). Called the (RSPH6A) is an ortholog of Chlamydomonas RSP6 in the RS head axoneme, this structure consists of macromolecular complexes such and is evolutionarily conserved. While some RS head proteins have as the outer and inner dynein arms and radial spokes (RSs) been linked to PCD, little is known about RSPH6A. Here, we show that (Fig. 1A). mouse RSPH6A is testis-enriched and localized in the flagellum. First characterized in sea urchins (Afzelius, 1959), the RS is a Rsph6a knockout (KO) male mice are infertile as a result of their short T-shaped protein complex that extends from the doublet immotile spermatozoa. -
Erdj4 Protein Is a Soluble Endoplasmic Reticulum (ER) Dnaj
Supplemental Material can be found at: http://www.jbc.org/content/suppl/2012/01/20/M111.311290.DC1.html THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 11, pp. 7969–7978, March 9, 2012 © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. ERdj4 Protein Is a Soluble Endoplasmic Reticulum (ER) DnaJ Family Protein That Interacts with ER-associated Degradation Machinery*□S Received for publication, October 6, 2011, and in revised form, January 5, 2012 Published, JBC Papers in Press, January 20, 2012, DOI 10.1074/jbc.M111.311290 Chunwei Walter Lai‡1,2, Joel H. Otero§1,3, Linda M. Hendershot§3, and Erik Snapp‡4 From the ‡Department of Anatomy & Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461 and the §Department of Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105 Background: ERdj4 is an endoplasmic reticulum chaperone co-factor that assists with destruction of misfolded secretory proteins. Results: ERdj4 is a mobile soluble luminal protein that is recruited to the misfolded secretory protein quality control machinery. Conclusion: The role of ERdj4 in secretory protein destruction is specified by association with the degradation machinery. Downloaded from Significance: These studies provide a new insight into how different ERdj family members regulate the fates of their clients. Protein localization within cells regulates accessibility for strates reflects a combination of subcellular localization, abun- interactions with co-factors and substrates. The endoplasmic dance, and the mobilities of both the protein and its substrates. reticulum (ER) BiP co-factor ERdj4 is up-regulated by ER stress For example, a freely and rapidly diffusing protein can readily www.jbc.org and has been implicated in ER-associated degradation (ERAD) encounter a substrate, even if the substrate is relatively immo- of multiple unfolded secretory proteins. -
Direction of Sliding and Relative Sliding Velocities Within Trypsinized Sperm Axonemes of Gallus Domesticus
Direction of sliding and relative sliding velocities within trypsinized sperm axonemes of Gallus domesticus DAVID M. WOOL LEY and ANDREW BRAMMALL* Department ofl'liysioloi>y. The Medical School, L'niversity of Bristol, Bristol BSS ITD, L'K •Present address: MRC Experimental Embryology and Teratology Unit, Medical Research Council Laboratories, Carshalton, Surrev SMS 4EF, UK Summary Trypsin digestion of demembranated fowl sper- orderly way by inter-doublet sliding. All the matozoa caused a longitudinal splitting of the doublets of the axoneme could be reactivated and distal part of the axoneme. The resulting strands, in all instances the direction of sliding was the consisting of groups of doublet microtubules, same as that reported for the cilia of Tetrahy- formed left-handed helices. On the evidence of tnena. Within the groups of doublets the electron micrographs, the digestion had caused measured inter-doublet displacements were gen- the loss of dynein arms from the outer row; it is erally similar, suggesting that the rates of sliding assumed that the doublets remained linked had been equivalent. These findings are con- together by dynein arms of the inner row. When trasted with the differential pattern of activation such helices were mechanically detached from that is assumed to occur in vivo. the proximal flagellum and reactivated with ad- Key words: Gallus domestic/is, sperm axonemes, sliding enosine triphosphate, they lengthened in an velocity. Introduction We have therefore made use of these preparations to study two aspects of the sliding behaviour relevant to It is well established that the motion of eukaryotic cilia the question of control and coordination.