10779/crick.12464810.v1 Marta I Budzinska Marta I Budzinska David Villarroel-Campos David Villarroel-Campos Matthew Golding Matthew Golding Anne Weston Anne Weston Lucy Collinson Lucy Collinson Ambrosius P Snijders Ambrosius P Snijders Giampietro Schiavo Giampietro Schiavo PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors. The Francis Crick Institute 2020 Intracellular sorting Motor neuron Trafficking TrkB p75NTR EM PRT Developmental Biology 06 Biological Sciences 11 Medical and Health Sciences 2020-06-25 13:47:14 Journal contribution https://crick.figshare.com/articles/journal_contribution/PTPN23_binds_the_dynein_adaptor_BICD1_and_is_required_for_endocytic_sorting_of_neurotrophin_receptors_/12464810 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.