PT  - JOURNAL ARTICLE
AU  - Afra Aabdien
AU  - Laura Sichlinger
AU  - Nicholas J.F. Gatford
AU  - Pooja Raval
AU  - Madeleine R. Jones
AU  - Lloyd Tanangonan
AU  - Timothy R. Powell
AU  - Rodrigo R.R. Duarte
AU  - Deepak P. Srivastava
TI  - Schizophrenia Risk Proteins ZNF804A and NT5C2 Interact at Synapses
AID  - 10.1101/2021.03.31.437821
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.31.437821
4099  - http://biorxiv.org/content/early/2021/03/31/2021.03.31.437821.short
4100  - http://biorxiv.org/content/early/2021/03/31/2021.03.31.437821.full
AB  - The zinc finger protein 804A (ZNF804A) and the 5′-nucleotidase cytosolic II (NT5C2) genes have been identified as robust susceptibility genes in large-scale genome-wide association studies of schizophrenia. The ZNF804A and NT5C2 proteins are highly expressed in developing and mature cortical neurons. ZNF804A has been implicated in regulating the development of neuronal morphology; it localises to synapses and is required for activity-dependent modifications of dendritic spines. NT5C2 has been shown to regulate 5′ adenosine monophosphate-activated protein kinase activity and implicated in influencing protein synthesis in neural progenitor cells. But despite these findings, a better understanding of the role these proteins play in regulating neuronal function is needed. A recent yeast two-hybrid screen has identified ZNF804A and NT5C2 as potential interacting proteins, but whether this occurs in situ; and moreover, in cortical neurons, is unknown. Here we show that ZNF804A and Nt5C2 colocalise and interact in hEK293T cells. Furthermore, their rodent homolouges, ZFP804A and NT5C2, specifically colocalise at synapses and form a protein complex in cortical neurons. Knockdown of Zfp804A or Nt5c2 resulted in a significant decrease in synaptic expression of both proteins, suggesting that both proteins are required for the synaptic targeting of each other. Taken together, these data indicate that ZNF804A/ZFP804A and NT5C2 interact together in cortical neurons and indicate that these GWAS risk factors may function as a complex to regulate neuronal function.Competing Interest StatementThe authors have declared no competing interest.