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LRRK2 Is Recruited to Phagosomes and Co-recruits RAB8 and RAB10 in Human Pluripotent Stem Cell-Derived Macrophages.
Lee, Heyne; Flynn, Rowan; Sharma, Ishta; Haberman, Emma; Carling, Phillippa J; Nicholls, Francesca J; Stegmann, Monika; Vowles, Jane; Haenseler, Walther; Wade-Martins, Richard; James, William S; Cowley, Sally A.
Afiliação
  • Lee H; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Flynn R; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Sharma I; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Haberman E; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Carling PJ; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
  • Nicholls FJ; Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, UK.
  • Stegmann M; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Vowles J; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
  • Haenseler W; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Wade-Martins R; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
  • James WS; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
  • Cowley SA; Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Electronic address: sally.cowley@path.ox.ac.uk.
Stem Cell Reports ; 14(5): 940-955, 2020 05 12.
Article em En | MEDLINE | ID: mdl-32359446
ABSTRACT
The Parkinson's disease-associated gene, LRRK2, is also associated with immune disorders and infectious disease and is expressed in immune subsets. Here, we characterize a platform for interrogating the expression and function of endogenous LRRK2 in authentic human phagocytes using human induced pluripotent stem cell-derived macrophages and microglia. Endogenous LRRK2 is expressed and upregulated by interferon-γ in these cells, including a 187-kDa cleavage product. Using LRRK2 knockout and G2019S isogenic repair lines, we find that LRRK2 is not involved in initial phagocytic uptake of bioparticles but is recruited to LAMP1+/RAB9+ "maturing" phagosomes, and LRRK2 kinase inhibition enhances its residency at the phagosome. Importantly, LRRK2 is required for RAB8a and RAB10 recruitment to phagosomes, implying that LRRK2 operates at the intersection between phagosome maturation and recycling pathways in these professional phagocytes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fagossomos / Proteínas rab de Ligação ao GTP / Células-Tronco Pluripotentes Induzidas / Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina / Macrófagos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fagossomos / Proteínas rab de Ligação ao GTP / Células-Tronco Pluripotentes Induzidas / Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina / Macrófagos Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article