Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin
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The Role of Coronin-1 in Neurotrophin Signaling During Sympathetic Nervous System Development
1 The role of Coronin-1 in neurotrophin signaling during sympathetic nervous system development Dong SUO Shaanxi, China Bachelor of Science, Zhejiang University, 2010 A Dissertation presented to the Graduate Faculty of the University of Virginia in Candidacy for the Degree of Doctor of Philosophy Department of Biology University of Virginia December, 2014 2 Abstract Long-distance signaling is a property inherent to neurons and neural circuits. Communication between axonal targets and neuronal cell bodies is increasingly recognized as critical for developmental processes and for normal function in adulthood. How this retrograde long-distance signal maintains high fidelity as it traffics to the cell body remains unknown, but could be achieved by the enhanced signal durations observed in some growth factor signaling. I found that the retrograde Nerve growth factor (NGF)-TrkA signaling endosome recruits a novel effector protein known as Coronin-1, which protects the endosome from lysosomal degradation during development. Indeed, in the absence of Coronin-1, the NGF-TrkA signaling endosome fuses to lysosomes 6-10-fold faster than in wild-type neurons. Furthermore, loss of Coronin-1 affects several NGF- dependent processes including neuron survival. These phenotypes are consistent with the finding that Coronin-1 stabilizes the NGF-TrkA signaling endosome, providing a plausible mechanism for long-distance retrograde signaling. Further, I demonstrated that Coronin-1 protects the signaling endosome by facilitating NGF-dependent calcium release and subsequent calcineurin activation. This novel mechanism for NGF-dependent calcium release provides insight into the mechanistic details underlying NGF-dependent transcription, axon growth, and cell survival. Above all, my findings argue for a critical role for Coronin-1 in sympathetic nervous system development. -
The Role of the Actin-Regulatory Proteins Coronin 1A and Coronin 1B in the Regulation of Natural Killer Cell Development and Function
Aus dem Forschungszentrum Borstel Leibniz-Zentrum für Medizin und Biowissenschaften Programmbereich Asthma & Allergie Forschungsgruppe Immunbiologie THE ROLE OF THE ACTIN-REGULATORY PROTEINS CORONIN 1A AND CORONIN 1B IN THE REGULATION OF NATURAL KILLER CELL DEVELOPMENT AND FUNCTION DISSERTATION zur Erlangung des Doktorgrades der Mathematisch-Naturwissenschaftliche Fakultät der Christian-Albrechts-Universität zu Kiel vorgelegt von André Jenckel Bad Segeberg, 2013 Erste/r Gutachter/in: Prof. Dr. Dr. Silvia Bulfone-Paus Zweite/r Gutachter/in: Prof. Dr. Thomas Roeder Tag der mündlichen Prüfung: 09.01.2014 Zum Druck genehmigt: 09.01.2014 gez. Prof. Dr. Wolfgang J. Duschl, Dekan Table of contents II Table of contents Table of contents ................................................................................................................. II Abbreviations ..................................................................................................................... VI List of figures...................................................................................................................... IX List of tables ....................................................................................................................... XI 1 Introduction .............................................................................................................. 1 1.1 The immune system ................................................................................................... 1 1.2 Natural killer cells ...................................................................................................... -
A Holistic Phylogeny of the Coronin Gene Family Reveals an Ancient
Eckert et al. BMC Evolutionary Biology 2011, 11:268 http://www.biomedcentral.com/1471-2148/11/268 RESEARCHARTICLE Open Access A holistic phylogeny of the coronin gene family reveals an ancient origin of the tandem-coronin, defines a new subfamily, and predicts protein function Christian Eckert, Björn Hammesfahr and Martin Kollmar* Abstract Background: Coronins belong to the superfamily of the eukaryotic-specific WD40-repeat proteins and play a role in several actin-dependent processes like cytokinesis, cell motility, phagocytosis, and vesicular trafficking. Two major types of coronins are known: First, the short coronins consisting of an N-terminal coronin domain, a unique region and a short coiled-coil region, and secondly the tandem coronins comprising two coronin domains. Results: 723 coronin proteins from 358 species have been identified by analyzing the whole-genome assemblies of all available sequenced eukaryotes (March 2011). The organisms analyzed represent most eukaryotic kingdoms but also cover every taxon several times to provide a better statistical sampling. The phylogenetic tree of the coronin domains based on the Bayesian method is in accordance with the most recent grouping of the major kingdoms of the eukaryotes and also with the grouping of more recently separated branches. Based on this “holistic” approach the coronins group into four classes: class-1 (Type I) and class-2 (Type II) are metazoan/ choanoflagellate specific classes, class-3 contains the tandem-coronins (Type III), and the new class-4 represents the coronins fused to villin (Type IV). Short coronins from non-metazoans are equally related to class-1 and class-2 coronins and thus remain unclassified. -
The Crystal Structure of Murine Coronin-1: a Regulator of Actin Cytoskeletal Dynamics in Lymphocytes
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Structure 14, 87–96, January 2006 ª2006 Elsevier Ltd All rights reserved DOI 10.1016/j.str.2005.09.013 The Crystal Structure of Murine Coronin-1: A Regulator of Actin Cytoskeletal Dynamics in Lymphocytes Brent A. Appleton,1 Ping Wu,1 SCAR proteins. They activate the Arp2/3 complex via and Christian Wiesmann1,* their verprolin-homology/cofilin-homology/acidic (VCA) 1 Department of Protein Engineering domain (reviewed in Millard et al., 2004). Like the Genentech, Inc. Arp2/3 complex, WASP is maintained in an inactive state South San Francisco, California 94080 with its VCA domain trapped in an autoinhibited confor- mation. Binding of cdc42 GTPase to WASP results in the release of the VCA domain, which ultimately leads to Summary WASP activation (Kim et al., 2000). In addition to positive signals to control the temporal and spatial activation Mammalian coronin-1 is preferentially expressed in of Arp2/3 within the cell, negative signals are required. hematopoietic cells and plays a poorly understood role However, while a detailed understanding of the pro- in the dynamic reorganization of the actin cytoskel- cesses that lead to Arp2/3 complex activation has eton. Sequence analysis of coronin-1 revealed five emerged, little is known about factors that mediate the WD40 repeats that were predicted to form a b propeller. downregulation of the complex. They are followed by a 130 residue extension and a 30 One class of proteins that are important for the residue leucine zipper domain that is responsible for downregulation of the Arp2/3 complex is the coronins multimerization of the protein. -
NIH Public Access Author Manuscript Trends Cell Biol
NIH Public Access Author Manuscript Trends Cell Biol. Author manuscript; available in PMC 2012 August 1. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Trends Cell Biol. 2011 August ; 21(8): 481±488. doi:10.1016/j.tcb.2011.04.004. Unraveling the enigma: Progress towards understanding the Coronin family of actin regulators Keefe T. Chan*, Sarah J. Creed*, and James E. Bear# Lineberger Comprehensive Cancer Center and Department of Cell & Developmental Biology Howard Hughes Medical Institute University of North Carolina at Chapel Hill Chapel Hill, NC 27599 USA Abstract Coronins are a conserved family of actin cytoskeleton regulators that promote cell motility and modulate other actin-dependent processes. Although these proteins have been known for twenty years, substantial progress has been made in the last five years towards understanding coronins. Here, we review this progress, place it into the context of what was already known and pose several questions that remain to be addressed. In particular, we cover the emerging consensus about the role of Type I coronins in coordinating the function of Arp2/3 complex and ADF/cofilin proteins. This coordination plays an important role in leading edge actin dynamics and overall cell motility. Finally, we discuss the roles played by the more exotic coronins of the Type II and III classes in cellular processes away from the leading edge. A brief natural history of coronins Coronins have been reviewed twice on the pages of Trends in Cell Biology, first in 1999 and again in 2006 1, 2. Here, we will provide an update on the progress made in the last five years of research on the coronin family. -
The Coronin Family and Human Disease
Send Orders for Reprints to [email protected] Current Protein and Peptide Science, 2016, 17, 000-000 1 The Coronin Family and Human Disease Xiaolong Liua,*, Yunzhen Gaoa, Xiao Linb, Lin Lia,b, Xiao Hanc and Jingfeng Liua,b aThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China; bThe First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People’s Republic c of China; Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing Please provide corresponding author(s) 100081, People’s Republic of China photograph size should be 4" x 4" inches Abstract: The Coronin family is one of the WD-repeat domain containing families that are diverse in both of their structures and functions. The first coronin was identified in the cytoskeleton composition of Dictyostelium discoideum, which was discovered to regulate the actin functions. So far, 723 coron- ins have been identified throughout the eukaryotic kingdom by bioinformatics analysis in 358 species. In mammals, 7 coronins have been identified to date, which are named through Coronin 1 to Coronin 7; all of these iso- forms contain two structurally conservational region: a 7-bladed β-propeller scaffold in N-terminal and a C-terminal vari- able coiled coil domain. Although some studies were showing that mammalian coronins have regulated the actin dynam- ics, recently many other functions such as calcium signaling regulation, cAMP signaling regulation, have been also re- ported beyond the actin modulation. Furthermore, many diseases have been found to be extensively associated with the abnormal expression of coronins, such as auto-immunity, bacterial and virus infection, neuronal behavior disorder and cancer.