PDR-1/hParkin negatively regulates the phagocytosis of apoptotic cell corpses in Caenorhabditis elegans

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...

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Detalhes bibliográficos
Autores: Cabello Gallardo, Juan, Sämann, J., Gómez-Orte, E., Erazo, Tatiana|||0000-0003-2355-0999, Coppa, A., Pujol, Aurora|||0000-0002-9606-0600, Büssing, I, Schulze, B., Lizcano de Vega, José Miguel|||0000-0002-3154-5383, Ferrer, I, Baumeister, R., Dalfo, Esther|||0000-0003-4677-8515
Formato: artículo
Fecha de publicación:2014
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:185015
Acesso em linha:https://ddd.uab.cat/record/185015
https://dx.doi.org/urn:doi:10.1038/cddis.2014.57
Access Level:acceso abierto
Palavra-chave:Parkin
Rac1
C. elegans
Engulfment
Proteasomal degradation
Descrição
Resumo: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.