DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling

Millar, J. Kirsty; Pickard, Ben; Mackie, Shaun; James, Rachel; Christie, Sheila; Buchanan, Sebastienne R.; Malloy, M. P.; Chubb, Jennifer E.; Huston, Elaine; Baillie, George S.; Thomson, Pippa A.; Hill, Elaine V.; Brandon, Nicholas J.; Rain, Jean‐Christophe; Camargo, Luiz Miguel; Whiting, Paul J.; Houslay, Miles D.; Blackwood, Douglas; Muir, Walter; Porteous, David J.

doi:10.1126/science.1112915

articleScienceNov 18, 2005Closed access

DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling

JKJ. Kirsty Millar BPBen Pickard SMShaun Mackie RJRachel James SCSheila Christie

Royal Edinburgh Hospital · Edinburgh Cancer Research · +5 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

The disrupted in schizophrenia 1 (DISC1) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role in the disorder is unknown. Here we report that the gene encoding phosphodiesterase 4B (PDE4B) is disrupted by a balanced translocation in a subject diagnosed with schizophrenia and a relative with chronic psychiatric illness. The PDEs inactivate adenosine 3',5'-monophosphate (cAMP), a second messenger implicated in learning, memory, and mood. We show that DISC1 interacts with the UCR2 domain of PDE4B and that elevation of cellular cAMP leads to dissociation of PDE4B from DISC1 and an increase in PDE4B activity. We propose a mechanistic model whereby DISC1 sequesters PDE4B in resting…

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650

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FWCI: 21.10
Percentile: 100%
References: 20

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Topics & keywords

Topics

Keywords

DISC1
Schizophrenia (object-oriented programming)
Phosphodiesterase
Cyclic adenosine monophosphate
Gene
Biology
Psychology
Genetics

UN Sustainable Development Goals

Good health and well-being

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