PMID- 23486974
OWN - NLM
STAT- MEDLINE
DCOM- 20130506
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 11
DP  - 2013 Mar 13
TI  - Postsynaptic density scaffold SAP102 regulates cortical synapse development 
      through EphB and PAK signaling pathway.
PG  - 5040-52
LID - 10.1523/JNEUROSCI.2896-12.2013 [doi]
AB  - Membrane-associated guanylate kinases (MAGUKs), including SAP102, PSD-95, PSD-93, 
      and SAP97, are scaffolding proteins for ionotropic glutamate receptors at 
      excitatory synapses. MAGUKs play critical roles in synaptic plasticity; however, 
      details of signaling roles for each MAGUK remain largely unknown. Here we report 
      that SAP102 regulates cortical synapse development through the EphB and PAK 
      signaling pathways. Using lentivirus-delivered shRNAs, we found that SAP102 and 
      PSD-95, but not PSD-93, are necessary for excitatory synapse formation and 
      synaptic AMPA receptor (AMPAR) localization in developing mouse cortical neurons. 
      SAP102 knockdown (KD) increased numbers of elongated dendritic filopodia, which 
      is often observed in mouse models and human patients with mental retardation. 
      Further analysis revealed that SAP102 coimmunoprecipitated the receptor tyrosine 
      kinase EphB2 and RacGEF Kalirin-7 in neonatal cortex, and SAP102 KD reduced 
      surface expression and dendritic localization of EphB. Moreover, SAP102 KD 
      prevented reorganization of actin filaments, synapse formation, and synaptic 
      AMPAR trafficking in response to EphB activation triggered by its ligand ephrinB. 
      Last, p21-activated kinases (PAKs) were downregulated in SAP102 KD neurons. These 
      results demonstrate that SAP102 has unique roles in cortical synapse development 
      by mediating EphB and its downstream PAK signaling pathway. Both SAP102 and PAKs 
      are associated with X-linked mental retardation in humans; thus, synapse 
      formation mediated by EphB/SAP102/PAK signaling in the early postnatal brain may 
      be crucial for cognitive development.
FAU - Murata, Yasunobu
AU  - Murata Y
AD  - McGovern Institute for Brain Research, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts 02139, USA. ymurata@mit.edu
FAU - Constantine-Paton, Martha
AU  - Constantine-Paton M
LA  - eng
GR  - R01 EY014074/EY/NEI NIH HHS/United States
GR  - 5R01EY014074-18/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg3 protein, rat)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Kalrn protein, rat)
RN  - 0 (Membrane Proteins)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (Receptors, Eph Family)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Age Factors
MH  - Analysis of Variance
MH  - Animals
MH  - Biotinylation
MH  - Cells, Cultured
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - Disks Large Homolog 4 Protein
MH  - Embryo, Mammalian
MH  - Female
MH  - Gene Expression Regulation, Developmental/genetics
MH  - Genetic Vectors/physiology
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Guanine Nucleotide Exchange Factors/metabolism
MH  - Humans
MH  - Immunoprecipitation
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Lentivirus/genetics
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/physiology/ultrastructure
MH  - Neuropeptides/genetics/*metabolism
MH  - Post-Synaptic Density/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Receptors, Eph Family/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction/genetics/*physiology
MH  - Synapses/*physiology
MH  - Synaptosomes/metabolism
MH  - Transfection
MH  - *Visual Cortex/cytology/growth & development/metabolism
PMC - PMC3632365
MID - NIHMS455434
EDAT- 2013/03/15 06:00
MHDA- 2013/05/07 06:00
PMCR- 2013/09/13
CRDT- 2013/03/15 06:00
PHST- 2013/03/15 06:00 [entrez]
PHST- 2013/03/15 06:00 [pubmed]
PHST- 2013/05/07 06:00 [medline]
PHST- 2013/09/13 00:00 [pmc-release]
AID - 33/11/5040 [pii]
AID - 3827132 [pii]
AID - 10.1523/JNEUROSCI.2896-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Mar 13;33(11):5040-52. doi: 10.1523/JNEUROSCI.2896-12.2013.