Protein expression and oxidation in the hippocampus of neuronal nucleoredoxin knockout (Nestin-NXN-/-) versus floxed control mice (NXN-flfl)

ABSTRACT: Nucleoredoxin (NXN) is a thioredoxin-like member of the large group of redoxins which maintain redox balances in the cell. Its primary localization is the cytoplasm, and it is highly expressed in neurons. It has been described as a redox regulator of WNT signaling via maintenance of the redox balance of Disheveled (Dvl). Previous proteomic analyses in NXN-knockdown SH-SY5Y cells found a high fraction of reduced proteins involved in development and cell differentiation. The results suggested NXN mainly acted as oxidase under the culture conditions. The functions in vivo are not known, but full deletion of NXN is embryonically lethal owing to cranial deformities. We have generated mice with a pan-neuronal Nestin-Cre driven deletion of NXN (Nestin-NXN-/-) to study its functions in neurons. Nestin-NXN-/- develop normally and are healthy up to old age. They show a loss of exploratory and playful behavior but have no deficits of cognitive functions, social behavior or readouts of anxiety. Using a Yeast-2-Hybrid screen, calcium calmodulin kinase 2a was identified as interaction partner. Camk2a is crucial for long-term potentiation and thereby learning and memory but is also associated with psychiatric diseases, and it is regulated via redox modification of cysteines that impact on the autophosphorylation status of a critical threonine. Camk2a colocalized and co-precipitated with NXN and its activity depended on the presence of NXN. To further study the functions of NXN in neurons we performed a proteomic screen of the hippocampal proteome and the redox proteome using the BIAM switch method.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Ilka Wittig  

LAB HEAD: Irmgard Tegeder

PROVIDER: PXD024624 | Pride | 2021-09-10

REPOSITORIES: Pride