An association study of the HSPA8 gene polymorphisms with schizophrenia in a Polish population

Heat shock cognate 70 (HSC70/HSPA8) is considered to be a promising candidate gene for schizophrenia (SCZ) due to its many essential functions and potential neuroprotective properties in the CNS (e.g., HSC70 is involved in the turnover of the synaptic proteins, synaptic vesicle recycling, and neurotransmitter homeostasis). An alteration in the expression of HSPA8 in SCZ has been reported. This implies that the genetic variants of HSPA8 might contribute to schizophrenia pathogenesis. The present study attempted to determine whether HSPA8 polymorphisms are associated with a susceptibility to schizophrenia or whether they have an impact on the clinical parameters of the disease in a Polish population. A total of 1066 participants (406 patients and 660 controls) were recruited for the study. Five SNPs of the HSPA8 gene (rs2236659, rs1136141, rs10892958, rs1461496, and rs4936770) were genotyped using TaqMan assays. There were no differences in the allele or genotype distribution in any of the SNPs in the entire sample. We also did not find any HSPA8 haplotype-specific associations with SCZ. A gender stratification analysis revealed that an increasing risk of schizophrenia was associated with the rs1461496 genotype in females (OR: 1.68, p < 0.05) in the recessive model. In addition, we found novel associations between HSPA8 SNPs (rs1136141, rs1461496, and rs10892958) and the severity of the psychiatric symptoms as measured by the PANSS. Further studies with larger samples from various ethnic groups are necessary to confirm our findings. Furthermore, studies that explore the functional contribution of the HSPA8 variants to schizophrenia pathogenesis are also needed.

Functional assessment of the V390F mutation in the CCTδ subunit of chaperonin containing tailless complex polypeptide 1

The chaperonin containing tailless complex polypeptide 1 (CCT) is a multi-subunit molecular chaperone. It is found in the cytoplasm of all eukaryotic cells, where the oligomeric form plays an essential role in the folding of predominantly the cytoskeletal proteins actin and tubulin. Both the CCT oligomer and monomeric subunits also display functions that extend beyond folding, which are often associated with microtubules and actin filaments. Here, we assess the functional significance of the CCTδ V390F mutation, reported in several cancer cell lines. Upon transfection into B16F1 mouse melanoma cells, GFP-CCTδV390F incorporates into the CCT oligomer more readily than GFP-CCTδ. Furthermore, unlike GFP-CCTδ, GFP-CCTδV390F does not interact with the dynactin complex component, p150Glued. As CCTδ has previously been implicated in altered migration in wound healing assays, we assessed the behaviour of GFP-CCTδV390F and other mutants of CCTδ, previously used to assess functional interactions with p150Glued, in chemotaxis assays. We developed the assay system to incorporate a layer of the inert hydrogel GrowDex® to provide a 3D matrix for chemotaxis assessment and found subtle differences in the migration of B16F1 cells, depending on the presence of the hydrogel.