An epilepsy-associated mutation in the nuclear import receptor KPNA7 reduces nuclear localization signal binding was written by Oostdyk, Luke T.;Wang, Zhenjia;Zang, Chongzhi;Li, Hui;McConnell, Michael J.;Paschal, Bryce M.. And the article was included in Scientific Reports in 2020.Reference of 11024-24-1 This article mentions the following:
KPNA7 is a member of the Importin-a family of nuclear import receptors. KPNA7 forms a complex with Importin-β and facilitates the translocation of signal-containing proteins from the cytoplasm to the nucleus. Exome sequencing of siblings with severe neurodevelopmental deffects and clin. features of epilepsy identified two amino acid-altering mutations in KPNA7. Here, we show that the E344Q substitution reduces KPNA7 binding to nuclear localization signals, and that this limits KPNA7 nuclear import activity. The P339A substitution, by contrast, has little effect on KPNA7 binding to nuclear localization signals. Given the neuronal phenotype described in the two patients, we used SILAC labeling, affinity enrichment, and mass spectrometry to identify KPNA7-interacting proteins in human induced pluripotent stem cell-derived neurons. We identified heterogeneous nuclear ribonucleoproteins hnRNP R and hnRNP U as KPNA7-interacting proteins. The E344Q substitution reduced binding and KPNA7-mediated import of these cargoes. The c.1030G > C allele which generates E344Q is within a predicted CTCF binding site, and we found that it reduces CTCF binding by approx. 40-fold. Our data support a role for altered neuronal expression and activity of KPNA7 in a rare type of pediatric epilepsy. In the experiment, the researchers used many compounds, for example, Digitonin (cas: 11024-24-1Reference of 11024-24-1).
Digitonin (cas: 11024-24-1) belongs to tetrahydropyran derivatives. Tetrahydropyrans and furans principally constitute as a central motif in diverse medicinally privileged molecules. The Prins reaction of homoallylic alcohols with aldehydes afforded an alternative method for the preparation of tetrahydropyrans.Reference of 11024-24-1
Referemce:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics