PMID- 28245069
OWN - NLM
STAT- MEDLINE
DCOM- 20170425
LR  - 20181113
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 45
IP  - 8
DP  - 2017 Apr
TI  - Synapsins regulate brain-derived neurotrophic factor-mediated synaptic 
      potentiation and axon elongation by acting on membrane rafts.
PG  - 1085-1101
LID - 10.1111/ejn.13552 [doi]
AB  - In neurons, intracellular membrane rafts are essential for specific actions of 
      brain-derived neurotrophic factor (BDNF), which include the regulation of axon 
      outgrowth, growth cone turning and synaptic transmission. Virtually, all the 
      actions of BDNF are mediated by binding to its receptor, TrkB. The association of 
      TrkB with the tyrosine kinase, Fyn, is critical for its localization to 
      intracellular membrane rafts. Here, we show that synapsins, a family of highly 
      amphipathic neuronal phosphoproteins, regulate membrane raft lipid composition 
      and consequently, the ability of BDNF to regulate axon/neurite development and 
      potentiate synaptic transmission. In the brains of mice lacking all synapsins, 
      the expression of both BDNF and TrkB were increased, suggesting that 
      BDNF/TrkB-mediated signaling is impaired. Consistent with this finding, 
      synapsin-depleted neurons exhibit altered raft lipid composition, deficient 
      targeting of Fyn to rafts, attenuated TrkB activation, and abrogation of 
      BDNF-stimulated axon outgrowth and synaptic potentiation. Conversely, 
      overexpression of synapsins in neuroblastoma cells results in corresponding 
      reciprocal changes in raft lipid composition, increased localization of Fyn to 
      rafts and promotion of BDNF-stimulated neurite formation. In the presence of 
      synapsins, the ratio of cholesterol to estimated total phospholipids converged to 
      1, suggesting that synapsins act by regulating the ratio of lipids in 
      intracellular membranes, thereby promoting lipid raft formation. These studies 
      reveal a mechanistic link between BDNF and synapsins, impacting early development 
      and synaptic transmission.
CI  - (c) 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Kao, Hung-Teh
AU  - Kao HT
AUID- ORCID: 0000-0002-5005-1493
AD  - Department of Psychiatry and Human Behavior, Brown University, 171 Meeting 
      Street, Room 187, Providence, RI, 02912, USA.
AD  - Butler Hospital, Providence, RI, USA.
FAU - Ryoo, Kanghyun
AU  - Ryoo K
AD  - Center for Functional Connectomics, Korea Institute of Science and Technology, 
      Sungbukgu, Seoul, Korea.
FAU - Lin, Albert
AU  - Lin A
AD  - Department of Psychiatry and Human Behavior, Brown University, 171 Meeting 
      Street, Room 187, Providence, RI, 02912, USA.
AD  - Butler Hospital, Providence, RI, USA.
FAU - Janoschka, Stephen R
AU  - Janoschka SR
AD  - Department of Psychiatry and Human Behavior, Brown University, 171 Meeting 
      Street, Room 187, Providence, RI, 02912, USA.
AD  - Butler Hospital, Providence, RI, USA.
FAU - Augustine, George J
AU  - Augustine GJ
AD  - Center for Functional Connectomics, Korea Institute of Science and Technology, 
      Sungbukgu, Seoul, Korea.
AD  - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 
      Singapore.
FAU - Porton, Barbara
AU  - Porton B
AD  - Department of Psychiatry and Human Behavior, Brown University, 171 Meeting 
      Street, Room 187, Providence, RI, 02912, USA.
AD  - Butler Hospital, Providence, RI, USA.
LA  - eng
GR  - P20 RR018728/RR/NCRR NIH HHS/United States
GR  - P30 GM103410/GM/NIGMS NIH HHS/United States
GR  - P30 RR031153/RR/NCRR NIH HHS/United States
GR  - R01 NS047209/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170321
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Phospholipids)
RN  - 0 (Synapsins)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.2 (FYN protein, human)
RN  - EC 2.7.10.2 (Fyn protein, mouse)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins c-fyn)
SB  - IM
MH  - Animals
MH  - Brain/cytology/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Enlargement
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - Humans
MH  - Membrane Microdomains/*metabolism
MH  - Membrane Potentials/*physiology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuroglia/cytology/metabolism
MH  - Neurons/*metabolism/physiology
MH  - Phospholipids/metabolism
MH  - Proto-Oncogene Proteins c-fyn/metabolism
MH  - Receptor, trkB/metabolism
MH  - Synapses/*metabolism
MH  - Synapsins/genetics/*metabolism
MH  - Synaptic Transmission/physiology
PMC - PMC5450799
MID - NIHMS856116
OTO - NOTNLM
OT  - lipid
OT  - mouse
OT  - neurodevelopment
OT  - signal transduction
COIS- Conflict of Interest Statement All authors indicate no potential conflicts of 
      interest.
EDAT- 2017/03/01 06:00
MHDA- 2017/04/26 06:00
PMCR- 2018/04/01
CRDT- 2017/03/01 06:00
PHST- 2015/08/20 00:00 [received]
PHST- 2017/01/27 00:00 [revised]
PHST- 2017/02/15 00:00 [accepted]
PHST- 2017/03/01 06:00 [pubmed]
PHST- 2017/04/26 06:00 [medline]
PHST- 2017/03/01 06:00 [entrez]
PHST- 2018/04/01 00:00 [pmc-release]
AID - 10.1111/ejn.13552 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2017 Apr;45(8):1085-1101. doi: 10.1111/ejn.13552. Epub 2017 Mar 
      21.