PMID- 24920579
OWN - NLM
STAT- MEDLINE
DCOM- 20140919
LR  - 20231213
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 33
IP  - 14
DP  - 2014 Jul 17
TI  - Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin 
      receptors.
PG  - 1582-98
LID - 10.15252/embj.201387579 [doi]
AB  - 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.
CI  - (c) 2014 The Authors.
FAU - Terenzio, Marco
AU  - Terenzio M
AD  - Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research 
      Institute, London, UK giampietro.schiavo@ucl.ac.uk marco.terenzio@weizmann.ac.il.
FAU - Golding, Matthew
AU  - Golding M
AD  - Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research 
      Institute, London, UK.
FAU - Russell, Matthew R G
AU  - Russell MR
AD  - Electron Microscopy Laboratory, Cancer Research UK London Research Institute, 
      London, UK.
FAU - Wicher, Krzysztof B
AU  - Wicher KB
AD  - Developmental Genetics Laboratory, Cancer Research UK London Research Institute, 
      London, UK.
FAU - Rosewell, Ian
AU  - Rosewell I
AD  - Transgenic Services laboratory, Cancer Research UK London Research Institute, 
      London, UK.
FAU - Spencer-Dene, Bradley
AU  - Spencer-Dene B
AD  - Experimental Histopathology Laboratory, Cancer Research UK London Research 
      Institute, London, UK.
FAU - Ish-Horowicz, David
AU  - Ish-Horowicz D
AD  - Developmental Genetics Laboratory, Cancer Research UK London Research Institute, 
      London, UK.
FAU - Schiavo, Giampietro
AU  - Schiavo G
AD  - Molecular NeuroPathobiology Laboratory, Cancer Research UK London Research 
      Institute, London, UK Sobell Department of Motor Neuroscience & Movement 
      Disorders, UCL-Institute of Neurology, University College London, London, UK 
      giampietro.schiavo@ucl.ac.uk marco.terenzio@weizmann.ac.il.
LA  - eng
GR  - Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140611
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (bicaudal-D1 protein, mouse)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Line
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - Endosomes/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Immunohistochemistry
MH  - Luminescent Proteins
MH  - Mice
MH  - Microscopy, Electron, Transmission
MH  - *Models, Biological
MH  - Motor Neurons/*metabolism
MH  - Protein Transport/physiology
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Nerve Growth Factor/*metabolism
MH  - Signal Transduction/genetics/*physiology
MH  - Red Fluorescent Protein
PMC - PMC4198053
OTO - NOTNLM
OT  - Bicd1
OT  - TrkB
OT  - intracellular sorting
OT  - neurotrophin signalling
OT  - p75NTR
EDAT- 2014/06/13 06:00
MHDA- 2014/09/23 06:00
PMCR- 2015/07/17
CRDT- 2014/06/13 06:00
PHST- 2014/06/13 06:00 [entrez]
PHST- 2014/06/13 06:00 [pubmed]
PHST- 2014/09/23 06:00 [medline]
PHST- 2015/07/17 00:00 [pmc-release]
AID - embj.201387579 [pii]
AID - 10.15252/embj.201387579 [doi]
PST - ppublish
SO  - EMBO J. 2014 Jul 17;33(14):1582-98. doi: 10.15252/embj.201387579. Epub 2014 Jun 
      11.