Transgenic Carrying a Human Full-Length DISC1 Construct (UAS-) Showing Effects on Social Interaction Networks.

Disrupted in Schizophrenia 1 (DISC1) is a scaffold protein implicated in major mental illnesses including schizophrenia, with a significant negative impact on social life. To investigate if DISC1 affects social interactions in , we created transgenic flies with second or third chromosome insertions of the human full-length ( gene fused to a UAS promotor (UAS-). Initial characterization of the insertion lines showed unexpected endogenous expression of the DISC1 protein that led to various behavioral and neurochemical phenotypes.

Aggregation of Disrupted in Schizophrenia 1 arises from a central region of the protein.

An emerging approach to studying major mental illness is through proteostasis, with the identification of several proteins that form insoluble aggregates in the brains of patients. One of these is Disrupted in Schizophrenia 1 (DISC1), a neurodevelopmentally-important scaffold protein, and product of a classic schizophrenia risk gene. DISC1 aggregates have been detected in post mortem brain tissue from patients with schizophrenia, bipolar disorder and major depressive disorder, as well as various model systems, although the mechanism by which it aggregates is still unclear.

Co-Aggregation and Parallel Aggregation of Specific Proteins in Major Mental Illness.

Background: Disrupted proteostasis is an emerging area of research into major depressive disorder. Several proteins have been implicated as forming aggregates specifically in the brains of subsets of patients with psychiatric illnesses. These proteins include CRMP1, DISC1, NPAS3 and TRIOBP-1.

Mapping the Domain Structure and Aggregation Propensity of Proteins Using a Gateway Plasmid Vector System.

Some proteins represent members of conserved families, meaning that their domain structure can be easily predicted by comparison to homologous proteins whose structures have been solved experimentally. Many other proteins, however, do not share significant detectable homology with other proteins, often as results of high amounts of coiled-coil structure and/or intrinsically unstructured regions. These proteins include many whose aggregation is linked to human disease.

TRIOBP-1 Protein Aggregation Exists in Both Major Depressive Disorder and Schizophrenia, and Can Occur through Two Distinct Regions of the Protein.

The presence of proteinopathy, the accumulation of specific proteins as aggregates in neurons, is an emerging aspect of the pathology of schizophrenia and other major mental illnesses. Among the initial proteins implicated in forming such aggregates in these conditions is Trio and F-actin Binding Protein isoform 1 (TRIOBP-1), a ubiquitously expressed protein involved in the stabilization of the actin cytoskeleton. Here we investigate the insolubility of TRIOBP-1, as an indicator of aggregation, in brain samples from 25 schizophrenia patients, 25 major depressive disorder patients and 50 control individuals (anterior cingulate cortex, BA23).

Protein Aggregation of NPAS3, Implicated in Mental Illness, Is Not Limited to the V304I Mutation.

An emerging phenomenon in our understanding of the pathophysiology of mental illness is the idea that specific proteins may form insoluble aggregates in the brains of patients, in partial analogy to similar proteinopathies in neurodegenerative diseases. Several proteins have now been detected as forming such aggregates in the brains of patients, including DISC1, dysbindin-1 and TRIOBP-1. Recently, neuronal PAS domain protein 3 (NPAS3), a known genetic risk factor for schizophrenia, was implicated through a V304I point mutation in a family with major mental illness.

The TRIOBP Isoforms and Their Distinct Roles in Actin Stabilization, Deafness, Mental Illness, and Cancer.

The ( and ) gene encodes multiple proteins, which together play crucial roles in modulating the assembly of the actin cytoskeleton. Splicing of the gene is complex, with the two most studied TRIOBP protein isoforms sharing no overlapping amino acid sequence with each other. TRIOBP-1 (also known as TARA or TAP68) is a mainly structured protein that is ubiquitously expressed and binds to F-actin, preventing its depolymerization.