| Popis: |
Disrupted proteostasis and protein co-aggregation is a novel approach in studying underlying mechanisms of non-genetic onset of chronic mental illnesses and schizophrenia specifically. Here we studied the ability of Trio-Binding Protein 1 (TRIOBP-1), implicated as aggregating in schizophrenia, to recruit other proteins to co- aggregate by overexpressing them in neuroblastoma cells. It was our aim to determine whether TROBP-1 co-aggregates with other proteins implicated in mental illness (DISC1, CRMP1 Sv, NPAS3), and to discover if TRIOBP-1 can induce aggregation of its normal interaction partners. Our results show that overexpressed, aggregating wild type TRIOBP-1 recruits NDE1 to co-aggregate. Furthermore, TRIOBP-1 co-aggregates with DISC1, another protein implicated in mental illness, but not with CRMP1 Sv or NPAS3. Mutated TRIOBP-1 stabilises DISC1, while on the other hand DISC1 recruits mutated TRIOBP-1 to co-aggregate. We conclude that the co- aggregation of TRIOBP-1 is a highly specific process and potentially of significant relevance to mental illness. These newly discovered proteinopathies could serve as a potential biological markers and used for early schizophrenia diagnosis if discovered not to be limited to the brain. Protein co-aggregation may provide a valuable insight in underlaying mechanism of non-genetic schizophrenia onset. |
