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A study was conducted to examine the role of disrupted-in-schizophrenia-1 (DISC1) in chronic mental diseases (CMD). Findings revealed novel DISC1 self-association motifs and the necessity of their concerted action for orderly assembly.

The impact of the expansion of the octarepeat (OR) domain on the prion-like conformation of the prion protein (PrP) is discussed. The expansion is shown to affect the misfolding pathway of PrP, where as the folding pathway remains unaffected.

Spatially resolved Raman and UV-vis-NIR microspectroscopy is used as tools to study the preparation process of supported catalyst bodies. Detailed spectroscopic information on the local coordination geometry of two different metallic species along with their macro-distribution over the catalyst body is obtained.

Raman microscopy is applied to monitor the preparation of shaped Mo/Al2O3 catalysts. It is illustrated that the time-resolved in situ Raman microscopy can be used to study the physicochemical processes during the preparation of supported catalysts.

Genetic studies have established a role of disrupted-in-schizophrenia-1 (DISC1) in chronic mental diseases (CMD). Limited experimental data are available on the domain structure of the DISC1 protein although multiple interaction partners are known including a self-association domain within the middle part of DISC1 (residues 403-504). The DISC1 C-terminal domain is deleted in the original Scottish pedigree where DISC1 harbors two coiled-coil domains and disease-associated polymorphisms at 607 and 704, as well as the important nuclear distribution element-like I (NDEL1) binding site at residues 802-839. Here, we performed mutagenesis studies of the C-terminal domain of the DISC1 protein (residues 640-854) and analyzed the expressed constructs by biochemical and biophysical methods. We identified novel DISC1 self-association motifs and the necessity of their concerted action for orderly assembly: the region 765-854 composing a coiled-coil domain is a dimerization domain and the region 668-747 an oligomerization domain; dimerization was found to be a prerequisite for orderly assembly of oligomers. Consistent with this, disease-associated polymorphism C704 displayed a slightly higher oligomerization propensity. The heterogeneity of DISC1 multimers in vitro was confirmed with a monoclonal antibody binding exclusively to HMW multimers. We also identified C-terminal DISC1 fragments in human brains, suggesting that C-terminal fragments could carry out DISC1-dependent functions. When the DISC1 C-terminal domain was transiently expressed in cells, it assembled into a range of soluble and insoluble multimers with distinct fractions selectively binding NDEL1, indicating functionality. Our results suggest that assembly of the C-terminal domain is controlled by distinct domains including the disease-associated polymorphism 704 and is functional in vivo. [ABSTRACT FROM AUTHOR]