PMID- 17610817
OWN - NLM
STAT- MEDLINE
DCOM- 20070912
LR  - 20181113
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 55
IP  - 1
DP  - 2007 Jul 5
TI  - Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar 
      precursors.
PG  - 53-68
AB  - During development, neural precursors migrate in response to positional cues such 
      as growth factor gradients. However, the mechanisms that enable precursors to 
      sense and respond to such gradients are poorly understood. Here we show that 
      cerebellar granule cell precursors (GCPs) migrate along a gradient of 
      brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle 
      trafficking is critical for this chemotactic process. Activation of TrkB, the 
      BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient 
      gradient. The BDNF gradient stimulates endocytosis of TrkB and associated 
      signaling molecules, causing asymmetric accumulation of signaling endosomes at 
      the subcellular location where BDNF concentration is maximal. Thus, regulated 
      BDNF exocytosis and TrkB endocytosis enable precursors to polarize and migrate in 
      a directed fashion along a shallow BDNF gradient.
FAU - Zhou, Pengcheng
AU  - Zhou P
AD  - Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, 
      USA.
FAU - Porcionatto, Marimelia
AU  - Porcionatto M
FAU - Pilapil, Mariecel
AU  - Pilapil M
FAU - Chen, Yicheng
AU  - Chen Y
FAU - Choi, Yoojin
AU  - Choi Y
FAU - Tolias, Kimberley F
AU  - Tolias KF
FAU - Bikoff, Jay B
AU  - Bikoff JB
FAU - Hong, Elizabeth J
AU  - Hong EJ
FAU - Greenberg, Michael E
AU  - Greenberg ME
FAU - Segal, Rosalind A
AU  - Segal RA
LA  - eng
GR  - NS377057/NS/NINDS NIH HHS/United States
GR  - NS045500/NS/NINDS NIH HHS/United States
GR  - P01 HD18655/HD/NICHD NIH HHS/United States
GR  - R01 NS045500/NS/NINDS NIH HHS/United States
GR  - R01 NS037757/NS/NINDS NIH HHS/United States
GR  - P30 HD018655/HD/NICHD NIH HHS/United States
GR  - R01 NS037757-08/NS/NINDS NIH HHS/United States
GR  - R01 NS037757-09/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuropeptides)
RN  - 0 (Rac1 protein, mouse)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 3.6.5.2 (cdc42 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
CIN - Neuron. 2007 Jul 5;55(1):1-2. PMID: 17610810
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*physiology
MH  - Cell Movement/drug effects
MH  - Cerebellum/*cytology/drug effects
MH  - Chemotaxis/*drug effects
MH  - Cytoplasmic Granules/physiology
MH  - Endocytosis/drug effects
MH  - Endosomes/*physiology
MH  - Lentivirus/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neuropeptides/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction/*physiology
MH  - Stem Cells/drug effects
MH  - cdc42 GTP-Binding Protein/metabolism
MH  - rac GTP-Binding Proteins/metabolism
MH  - rac1 GTP-Binding Protein
MH  - rhoA GTP-Binding Protein/metabolism
PMC - PMC2661852
MID - NIHMS27124
EDAT- 2007/07/06 09:00
MHDA- 2007/09/13 09:00
PMCR- 2009/03/27
CRDT- 2007/07/06 09:00
PHST- 2006/01/23 00:00 [received]
PHST- 2006/11/08 00:00 [revised]
PHST- 2007/05/31 00:00 [accepted]
PHST- 2007/07/06 09:00 [pubmed]
PHST- 2007/09/13 09:00 [medline]
PHST- 2007/07/06 09:00 [entrez]
PHST- 2009/03/27 00:00 [pmc-release]
AID - S0896-6273(07)00444-8 [pii]
AID - 10.1016/j.neuron.2007.05.030 [doi]
PST - ppublish
SO  - Neuron. 2007 Jul 5;55(1):53-68. doi: 10.1016/j.neuron.2007.05.030.