The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.
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.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.(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.CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RanBP9-associated pathways.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, Tumor, Cytoskeletal Proteins, HeLa Cells, Humans, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Receptor, Cannabinoid, CB1, Schizophrenia
Adaptor Proteins, Signal Transducing, Cell Line, Tumor, Cytoskeletal Proteins, HeLa Cells, Humans, Nerve Tissue Proteins, Neurons, Nuclear Proteins, Receptor, Cannabinoid, CB1, Schizophrenia
Neuroscience
Date: Dec. 03, 2015
PubMed ID: 26475744
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