This new work is published here: https://www.jpeds.com/article/S0022-3476(21)00616-8/fulltext
About Lori Isom
This author has yet to write their bio.Meanwhile lets just say that we are proud Lori Isom contributed a whooping 17 entries.
Entries by Lori Isom
We met on the patio at The Session Room!
We are searching for postdoctoral fellows to work on our NIH-funded projects to understand neuro-cardiac mechanisms of developmental and epileptic encephalopathy with SUDEP. Successful applicants must have expertise in electrophysiological analysis of mouse cardiac myocytes, primary neurons, or brain slices and/or with human iPSC-derived neurons, brain organoids, or cardiac myocytes. Interested applicants: Please send a […]
Loss-of-function (LOF) variants in SCN1B, encoding voltage-gated sodium channel β1 subunits, are linked to human diseases with high risk of sudden death, including developmental and epileptic encephalopathy and cardiac arrhythmia. β1 Subunits modulate the cell-surface localization, gating, and kinetics of sodium channel pore-forming α subunits. They also participate in cell-cell and cell-matrix adhesion, resulting in intracellular signal transduction, promotion of cell migration, calcium handling, and regulation of cell morphology. Here, we investigated regulated intramembrane proteolysis (RIP) of β1 by BACE1 and γ-secretase and show that β1 subunits are substrates for sequential RIP by BACE1 and γ-secretase, resulting in the generation of a soluble intracellular domain (ICD) that is translocated to the nucleus. Using RNA sequencing, we identified a subset of genes that are downregulated by β1-ICD overexpression in heterologous cells but upregulated in Scn1b-null cardiac tissue, which lacks β1-ICD signaling, suggesting that the β1-ICD may normally function as a molecular brake on gene transcription in vivo. We propose that human disease variants resulting in SCN1B LOF cause transcriptional dysregulation that contributes to altered excitability. Moreover, these results provide important insights into the mechanism of SCN1B-linked channelopathies, adding RIP-excitation coupling to the multifunctionality of sodium channel β1 subunits.
This article was written by Professor David Henshall, Director of the FutureNeuro SFI Research Centre at the Royal College of Surgeons in Ireland.
Dr. Luis Lopez-Santiago was excited to receive his first COVID-19 vaccination dose.