DISC1

DISC1 is a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family.

Full Name

Disrupted in Schizophrenia 1

Function

Involved in the regulation of multiple aspects of embryonic and adult neurogenesis (PubMed:19502360, PubMed:19303846).

Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus (By similarity).

Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance (PubMed:19303846).

Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation (By similarity).

Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A (By similarity).

Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development (PubMed:19502360).

Inhibits ATF4 transcription factor activity in neurons by disrupting ATF4 dimerization and DNA-binding (By similarity).

Plays a role, together with PCNT, in the microtubule network formation (PubMed:18955030).

Biological Process

Canonical Wnt signaling pathway Source: Ensembl
Cell proliferation in forebrain Source: Ensembl
Cilium assembly Source: GO_Central
Microtubule cytoskeleton organization Source: UniProtKB
Mitochondrial calcium ion homeostasis Source: Ensembl
Negative regulation of protein binding Source: ARUK-UCL
Neuron migration Source: UniProtKB
Non-motile cilium assembly Source: SYSCILIA_CCNET
Positive regulation of axon extension Source: Ensembl
Positive regulation of cell-matrix adhesion Source: Ensembl
Positive regulation of neuroblast proliferation Source: UniProtKB
Positive regulation of neuron projection development Source: Ensembl
Positive regulation of ubiquitin-dependent protein catabolic process Source: Ensembl
Positive regulation of Wnt signaling pathway Source: UniProtKB
Protein localization to centrosome Source: Ensembl
Pyramidal neuron migration Source: Ensembl
Regulation of dendritic spine development Source: Ensembl
Regulation of neuron projection development Source: GO_Central
Regulation of synapse maturation Source: Ensembl
Regulation of synaptic transmission, glutamatergic Source: Ensembl
Response to electrical stimulus Source: Ensembl
TOR signaling Source: Ensembl

Cellular Location

Mitochondrion; Cytoplasm; Cytoskeleton; Centrosome; Postsynaptic density. Colocalizes with NDEL1 in the perinuclear region and the centrosome (By similarity). Localizes to punctate cytoplasmic foci which overlap in part with mitochondria (PubMed:12506198, PubMed:15797709). Colocalizes with PCNT at the centrosome (PubMed:18955030).

Involvement in disease

A chromosomal aberration involving DISC1 segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 and NDEL1.
Schizophrenia 9 (SCZD9):
A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.

PTM

Ubiquitinated. Ubiquitination with 'Lys-48'-linked polyubiquitin chains leads to its proteasomal degradation.