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PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors.
Budzinska, Marta I; Villarroel-Campos, David; Golding, Matthew; Weston, Anne; Collinson, Lucy; Snijders, Ambrosius P; Schiavo, Giampietro.
Afiliação
  • Budzinska MI; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
  • Villarroel-Campos D; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
  • Golding M; William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
  • Weston A; Electron Microscopy, The Francis Crick Institute, 1 Midland Road, London NW1 1ST, UK.
  • Collinson L; Electron Microscopy, The Francis Crick Institute, 1 Midland Road, London NW1 1ST, UK.
  • Snijders AP; Proteomics Science Technology Platforms, The Francis Crick Institute, 1 Midland Road, London NW1 1ST, UK.
  • Schiavo G; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK giampietro.schiavo@ucl.ac.uk.
J Cell Sci ; 133(6)2020 03 30.
Article em En | MEDLINE | ID: mdl-32079660
Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand-receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75NTR (also known as NGFR) in motor neurons. Here, using a proteomics approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1-knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dineínas / Monoéster Fosfórico Hidrolases / Proteínas Tirosina Fosfatases não Receptoras Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dineínas / Monoéster Fosfórico Hidrolases / Proteínas Tirosina Fosfatases não Receptoras Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2020 Tipo de documento: Article