PMID- 25221472
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140915
LR  - 20211021
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 8
DP  - 2014
TI  - Mechanisms of NOS1AP action on NMDA receptor-nNOS signaling.
PG  - 252
LID - 10.3389/fncel.2014.00252 [doi]
LID - 252
AB  - NMDA receptors (NMDAR) are glutamate-gated calcium channels that play pivotal 
      roles in fundamental aspects of neuronal function. Dysregulated receptor function 
      contributes to many disorders. Recruitment by NMDARs of calcium-dependent enzyme 
      nNOS via PSD95 is seen as a key contributor to neuronal dysfunction. nNOS adaptor 
      protein (NOS1AP), originally described as a competitor of PSD95:nNOS interaction, 
      is regarded an inhibitor of NMDAR-driven nNOS function. In conditions of NMDAR 
      hyperactivity such as excitotoxicity, one expects NOS1AP to be neuroprotective. 
      Conditions of NMDAR hypoactivity, as thought to occur in schizophrenia, might be 
      exacerbated by NOS1AP. Indeed GWAS have implicated NOS1AP and nNOS in 
      schizophrenia. Several studies now indicate NOS1AP can mediate rather than 
      inhibit NMDAR/nNOS-dependent responses, including excitotoxic signaling. Yet the 
      concept of NOS1AP as an inhibitor of nNOS predominates in studies of human 
      disease genetics. Here we review the experimental evidence to evaluate this 
      apparent controversy, consider whether the known functions of NOS1AP might defend 
      neurons against NMDAR dysregulation and highlight specific areas for future 
      investigation to shed light on the functions of this adaptor protein.
FAU - Courtney, Michael J
AU  - Courtney MJ
AD  - Molecular Signalling Laboratory, Department of Neurobiology, A. I. Virtanen 
      Institute, University of Eastern Finland Kuopio, Finland ; Turku Centre for 
      Biotechnology, Abo Akademi University and University of Turku Turku, Finland.
FAU - Li, Li-Li
AU  - Li LL
AD  - Molecular Signalling Laboratory, Department of Neurobiology, A. I. Virtanen 
      Institute, University of Eastern Finland Kuopio, Finland.
FAU - Lai, Yvonne Y
AU  - Lai YY
AD  - Jack Gill Center for Biomolecular Science, Department Psychological and Brain 
      Sciences, Indiana University Bloomington, IN, USA.
LA  - eng
GR  - R21 DA037673/DA/NIDA NIH HHS/United States
GR  - R21 MH104018/MH/NIMH NIH HHS/United States
GR  - UL1 TR001108/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20140827
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC4145862
OTO - NOTNLM
OT  - NMDA receptor
OT  - NOS1AP
OT  - PDZ
OT  - PSD95
OT  - excitotoxicity
OT  - nNOS
OT  - nitric oxide
OT  - schizophrenia
EDAT- 2014/09/16 06:00
MHDA- 2014/09/16 06:01
PMCR- 2014/01/01
CRDT- 2014/09/16 06:00
PHST- 2014/07/07 00:00 [received]
PHST- 2014/08/07 00:00 [accepted]
PHST- 2014/09/16 06:00 [entrez]
PHST- 2014/09/16 06:00 [pubmed]
PHST- 2014/09/16 06:01 [medline]
PHST- 2014/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2014.00252 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2014 Aug 27;8:252. doi: 10.3389/fncel.2014.00252. 
      eCollection 2014.