Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors
| Autor: | Krzysztof B. Wicher, David Ish-Horowicz, Marco Terenzio, Giampietro Schiavo, Matthew Golding, Bradley Spencer-Dene, Ian Rosewell, Matthew R. G. Russell |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Endosome
Receptor expression Blotting Western Fluorescent Antibody Technique Tropomyosin receptor kinase B Endosomes Receptors Nerve Growth Factor Biology Real-Time Polymerase Chain Reaction Models Biological General Biochemistry Genetics and Molecular Biology Cell Line Mice Microscopy Electron Transmission Low-affinity nerve growth factor receptor Animals RNA Small Interfering Receptor Molecular Biology Adaptor Proteins Signal Transducing Brain-derived neurotrophic factor Motor Neurons General Immunology and Microbiology General Neuroscience Brain-Derived Neurotrophic Factor Articles Immunohistochemistry Cell biology Cytoskeletal Proteins Luminescent Proteins Protein Transport nervous system biology.protein Signal transduction Neurotrophin Signal Transduction |
| Popis: | We have identified a new function for the dynein adaptor Bicaudal D homolog 1 (BICD1) by screening a siRNA library for genes affecting the dynamics of neurotrophin receptor-containing endosomes in motor neurons (MNs). Depleting BICD1 increased the intracellular accumulation of brain-derived neurotrophic factor (BDNF)-activated TrkB 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 TrkB 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 BICD1 regulates neurotrophin signalling by modulating the endosomal sorting of internalised ligand-activated receptors. |
| Databáze: | OpenAIRE |
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