F200. elucidating the role of cilia in neuropsychiatric diseases through interactome analysis

DiscussionCiliary genes like DRD1 and DRD2 are implicated in neurotransmission and associated with schizophrenia. DRD1 has 4 novel interactors and DRD2 has 12 novel interactors that may have significant role in the pathology of mental disorders. Neuronal pathways associated with cilia interactome with high statistical significance such as dopamine signaling, eNOS signaling, synaptic long-term potentiation pathways are known to be associated schizophrenia. Wnt signaling and PCP signaling are also known to be associated with cilia mediated neurodevelopmental signaling, defects in these pathways contributing to schizophrenia. Novel interactions for cilia proteins validated by experiments have functional significance in association with cilia and neuronal disorders. For e.g., IFT88, a cilia protein required for cilia assembly, is critical for SHH signaling, cell cycle regulation and cerebellar development and is also associated with schizophrenia and bipolar disorder. CACNA1I is predicted to interact with DNAL4 and MKS1, both involved in transport of proteins required for ciliogenesis. GWAS studies show that CACNA1I is associated with schizophrenia. Taken together, the cilia interactome presented here provides novel insights into the relationship between ciliary protein function and neuropsychiatric diseases.
Source: Schizophrenia Bulletin - Category: Psychiatry Source Type: research