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PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors

Budzinska, MI; Villarroel-Campos, D; Golding, M; Weston, A; Collinson, L; Snijders, AP; Schiavo, G; (2020) PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors. Journal of Cell Science , 133 (6) , Article jcs242412. 10.1242/jcs.242412. Green open access

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Abstract

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 formation of signalling-competent ligand-receptor complexes, their endocytosis and trafficking. 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 and p75NTR in motor neurons. Here, using a proteomic 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.

Type: Article
Title: PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/jcs.242412
Publisher version: http://dx.doi.org/10.1242/jcs.242412
Language: English
Additional information: © 2020. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Intracellular sorting, Motor neuron, Trafficking, TrkB, p75NTR
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10092226
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