title: PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans.
abstract: Apoptotic cell death is an integral part of cell turnover in many tissues, and proper corpse clearance is vital to maintaining tissue homeostasis in all multicellular organisms. Even in tissues with high cellular turnover, apoptotic cells are rarely seen because of efficient clearance mechanisms in healthy individuals. In Caenorhabditis elegans, two parallel and partly redundant conserved pathways act in cell corpse engulfment. The pathway for cytoskeletal rearrangement requires the small GTPase CED-10 Rac1 acting for an efficient surround of the dead cell. The CED-10 Rac pathway is also required for the proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. Parkin, the mammalian homolog of the C. elegans PDR-1, interacts with Rac1 in aged human brain and it is also implicated with actin dynamics and cytoskeletal rearrangements in Parkinsons's disease, suggesting that it might act on engulfment. Our genetic and biochemical studies indicate that PDR-1 inhibits apoptotic cell engulfment and DTC migration by ubiquitylating CED-10 for degradation.
authors.affiliation: CIBIR (Centre for Biomedical Research of La Rioja), C/Piqueras 98, Logroño 26006, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Cabello
authors.affiliation: Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sämann
authors.affiliation: CIBIR (Centre for Biomedical Research of La Rioja), C/Piqueras 98, Logroño 26006, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gómez-Orte
authors.affiliation: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona 08193, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Erazo
authors.affiliation: Neurometabolic Diseases Laboratory, Institut D'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona 08907, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Coppa
authors.affiliation: 1] Neurometabolic Diseases Laboratory, Institut D'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona 08907, Spain [2] ICREA (Institució Catalana de Recerca i Estudis avançats), Barcelona, Spain [3] Institute of Neuropathology, University Hospitall Bellvitge - University of Barcelona - IDIBELL, L'Hospitalet de Llobregat, Ciberned, Spain [4] CIBERER (Centro de Investigación Biomédica en Enfermedades Raras), C/ Álvaro de Bazán, 10 Bajo, Valencia 46010, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Pujol
authors.affiliation: Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Büssing
authors.affiliation: Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Schulze
authors.affiliation: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Cerdanyola del Vallés, Barcelona 08193, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Lizcano
authors.affiliation: Institute of Neuropathology, University Hospitall Bellvitge - University of Barcelona - IDIBELL, L'Hospitalet de Llobregat, Ciberned, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: 1] Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany [2] Centre for Biological Signaling Studies (bioss), University of Freiburg, Freiburg 79104, Germany [3] FRIAS Freiburg Institute for Advanced Studies, Section Life Sciences (LIFENET), University of Freiburg, Schaenzlestrasse 1, Freiburg 79104, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Baumeister
authors.affiliation: 1] Bioinformatics and Molecular Genetics (Faculty of Biology), Center for Biochemistry and Molecular Cell Research (Faculty of Medicine), Schänzlestrasse 1, Freiburg 79104, Germany [2] Neurometabolic Diseases Laboratory, Institut D'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona 08907, Spain [3] Institute of Neuropathology, University Hospitall Bellvitge - University of Barcelona - IDIBELL, L'Hospitalet de Llobregat, Ciberned, Spain [4] CIBERER (Centro de Investigación Biomédica en Enfermedades Raras), C/ Álvaro de Bazán, 10 Bajo, Valencia 46010, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Dalfo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D010587:Phagocytosis / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D059748:Proteolysis; D015398:Signal Transduction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: C407268:CED-10 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D061988:Proteasome Inhibitors; C107953:RAC1 protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D046988:Proteasome Endopeptidase Complex; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein