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Bicaudal‐ D 1 regulates the intracellular sorting and signalling of neurotrophin receptors
Author(s) -
Terenzio Marco,
Golding Matthew,
Russell Matthew R G,
Wicher Krzysztof B,
Rosewell Ian,
SpencerDene Bradley,
IshHorowicz David,
Schiavo Giampietro
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201387579
Subject(s) - biology , receptor , microbiology and biotechnology , signalling , intracellular , neurotrophin , signal transduction , signalling pathways , genetics
We have identified a new function for the dynein adaptor Bicaudal D homolog 1 ( BICD 1) by screening a si RNA library for genes affecting the dynamics of neurotrophin receptor‐containing endosomes in motor neurons ( MN s). Depleting BICD 1 increased the intracellular accumulation of brain‐derived neurotrophic factor ( BDNF )‐activated T rk B and p75 neurotrophin receptor (p75 NTR ) by disrupting the endosomal sorting, reducing lysosomal degradation and increasing the co‐localisation of these neurotrophin receptors with retromer‐associated sorting nexin 1. The resulting re‐routing of active receptors increased their recycling to the plasma membrane and altered the repertoire of signalling‐competent T rk B isoforms and p75 NTR available for ligand binding on the neuronal surface. This resulted in attenuated, but more sustained, AKT activation in response to BDNF stimulation. These data, together with our observation that Bicd1 expression is restricted to the developing nervous system when neurotrophin receptor expression peaks, indicate that BICD 1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand‐activated receptors.