Mutations in DISC1 alter IP(3)R and voltage-gated Ca(2+) channel functioning, implications for major mental illness

Disrupted in Schizophrenia 1 (DISC1) participates in a wide variety of developmental processes of central neurons. It also serves critical roles that underlie cognitive functioning in adult central neurons. Here we summarize DISC1’s general properties and discuss its use as a model system for understanding major mental illnesses (MMIs). We then discuss the cellular actions of DISC1 that involve or regulate Ca(2+) signaling in adult central neurons. In particular, we focus on the tethering role DISC1 plays in transporting RNA particles containing Ca(2+) channel subunit RNAs, including IP3R1, CACNA1C and CACNA2D1, and in transporting mitochondria into dendritic and axonal processes. We also review DISC1’s role in modulating IP(3)R1 activity within mitochondria-associated ER membrane (MAM). Finally, we discuss DISC1-glycogen synthase kinase 3β (GSK3β) signaling that regulates functional expression of voltage-gated Ca(2+) channels (VGCCs) at central synapses. In each case, DISC1 regulates the movement of molecules that impact Ca(2+) signaling in neurons.