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Neuroscience. 2015 Dec 3;310:723-30. doi: 10.1016/j.neuroscience.2015.10.012. Epub 2015 Oct 22.

The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.

Author information

1
Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Electronic address: xiejcn@yahoo.com.
2
Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
3
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

PRINCIPAL FINDINGS:

(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.

CONCLUSION:

CCDC55 may be involved in a functional bridging between the CNR1 activation and the DISC1/RanBP9-associated pathways.

KEYWORDS:

Ran binding protein 9; cannabinoid receptor 1; cannabinoid receptor interacting protein 1a; coiled coil domain-containing 55; disrupted-in-schizophrenia 1; schizophrenia

[Indexed for MEDLINE]

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