RGD Reference Report - NOS1AP regulates dendrite patterning of hippocampal neurons through a carboxypeptidase E-mediated pathway. - Rat Genome Database

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NOS1AP regulates dendrite patterning of hippocampal neurons through a carboxypeptidase E-mediated pathway.

Authors: Carrel, D  Du, Y  Komlos, D  Hadzimichalis, NM  Kwon, M  Wang, B  Brzustowicz, LM  Firestein, BL 
Citation: Carrel D, etal., J Neurosci. 2009 Jun 24;29(25):8248-58.
RGD ID: 6483099
Pubmed: PMID:19553464   (View Abstract at PubMed)
PMCID: PMC2819070   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.5287-08.2009   (Journal Full-text)

During neuronal development, neurons form elaborate dendritic arbors that receive signals from axons. Additional studies are needed to elucidate the factors regulating the establishment of dendritic patterns. Our work explored possible roles played by nitric oxide synthase 1 adaptor protein (NOS1AP; also known as C-terminal PDZ ligand of neuronal nitric oxide synthase or CAPON) in dendritic patterning of cultured hippocampal neurons. Here we report that the long isoform of NOS1AP (NOS1AP-L) plays a novel role in regulating dendrite outgrowth and branching. NOS1AP-L decreases dendrite number when overexpressed at any interval between day in vitro (DIV) 0 and DIV 12, and knockdown of NOS1AP-L results in increased dendrite number. In contrast, the short isoform of NOS1AP (NOS1AP-S) decreases dendrite number only when overexpressed during DIV 5-7. Using mutants of NOS1AP-L, we show that neither the PDZ-binding domain nor the PTB domain is necessary for the effects of NOS1AP-L. We have functionally narrowed the region of NOS1AP-L that mediates this effect to the middle amino acids 181-307, a region that is not present in NOS1AP-S. Furthermore, we performed a yeast two-hybrid screen and identified carboxypeptidase E (CPE) as a binding partner for the middle region of NOS1AP-L. Biochemical and cellular studies reveal that CPE mediates the effects of NOS1AP on dendrite morphology. Together, our results suggest that NOS1AP-L plays an important role in the initiation, outgrowth, and maintenance of dendrites during development.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CpeRatnegative regulation of branching morphogenesis of a nerve  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CpeRatdense core granule  IDA  RGD 
CpeRatsynaptic membrane  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nos1apRatprotease binding  IPICpe (Rattus norvegicus) RGD 
CpeRatprotein binding  IPINos1ap (Rattus norvegicus) RGD 
CpeRatprotein domain specific binding  IDA Nos1apRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cpe  (carboxypeptidase E)
Nos1ap  (nitric oxide synthase 1 adaptor protein)


Additional Information