title: The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.
abstract: OBJECTIVE
  Our previous study suggested that the coiled coil domain-containing 55 gene (CCDC55), also named as NSRP1 (nuclear speckle splicing regulatory protein 1 (NSRP1)), was encompassed in a haplotype block spanning over the serotonin transporter (5-HTT) gene in patients with schizophrenia (SCZ). However, the neurobiological function of CCDC55 gene remains unknown. This study aims to uncover the potential role of CCDC55 in SCZ-associated molecular pathways.
  
  
  METHODS
  Using molecular cloning, sequencing and immune blotting to identify basic properties, yeast two-hybrid screening and glutathione S-transferase (GST) pull-down assay to test protein-protein interaction, and confocal laser scanning microscopy (CSLM) to show intracellular interaction of proteins.
  
  
  RESULTS
  (i) CCDC55 is expressed as a nuclear protein in human neuronal cells; (ii) Protein-protein interaction analyses showed CCDC55 physically interacted with Ran binding protein 9 (RanBP9) and disrupted in schizophrenia 1 (DISC1); (iii) CCDC55 and RanBP9 co-localized in the nucleus of human neuronal cells; (iv) CCDC55 also interacted with the cannabinoid receptor 1 (CNR1), and with the brain cannabinoid receptor-interacting protein 1a (CNRIP1a); (v) CNR1 activation in differentiated human neuronal cells resulted in an altered RanBP9 localization.
  
  
  CONCLUSIONS
  CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RanBP9-associated pathways.
authors.affiliation: Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Electronic address: xiejcn@yahoo.com.
authors.forename: J
authors.initials: J
authors.lastname: Xie
authors.affiliation: Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Gizatullin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Vukojevic
authors.affiliation: Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Leopardi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C571130:CNR1 protein, human; D003598:Cytoskeletal Proteins; C412476:DISC1 protein, human; C560091:NSRP1 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; D043884:Receptor, Cannabinoid, CB1
keywords: Ran binding protein 9; cannabinoid receptor 1; cannabinoid receptor interacting protein 1a; coiled coil domain-containing 55; disrupted-in-schizophrenia 1; schizophrenia