Jamie Stout
Pronouns: She/Her/Hers
Research Mentor(s): Gabriel Corfas
Research Mentor School/College/Department: Kesge Hearing Research Institute / Medicine
Program: UROP
Session: Session 2 (10:00am – 10:50am)
Authors: Jamie Stout, Mostafa Ibrahim
Abstract
ErbB4 is a transmembrane protein with two isoforms ErbB4-Jma and ErbB4-Jmb. While ErbB4-Jmb signals like all other known, Receptor Tyrosine Kinases (RTKs), i.e.,through a series of kinase cascades, ErbB4-Jma can signal by an additional mechanism now called non-canonical RTK signaling. In this case, after ErbB4-JMa activation by its ligand neuregulin induced by presenilin, a protease involved in Alzheimer’s disease. This presenilin-dependent cleavage results in the release of the ErbB4 intracellular domain known as E4ICD which translocates to the nucleus where it regulates transcription. PARP-1 is an ADP-ribosylating enzyme that controls major cellular and biological processes in cells (Ko, Hui Ling, and Ee Chee Ren). Here we explore whether or not there is an interaction between PARP-1 and E4ICD and how this supposed interaction impacts astrogenesis. Through the use of co-immunoprecipitation techniques it was possible to pull down intracellular domain E4ICD which were then used in western blots. We found that PARP-1 was co-immunoprecipitated with E4ICD in nuclear extracts of HEK cells transfected with plasmids of Jma, not Jmb, ErbB4 isoform. This implies interaction between PARP-1 and E4ICD. Following these procedures, qPCR was performed to detect the level of gene expression of GFAP which is an astrocyte marker in neural precursor stem cells (NPCs). It was demonstrated that the activation of ErbB4-Jma by neuregulin decreases astrogenesis while the absence of this increases astrogenesis. This experiment was also done in PARP-1 knockout neural precursors. In this sample, it was observed that ErbB4 activated by neuregulin without PARP-1 did not repress astrogenesis. This study has established an interaction between PARP-1 and ErbB4 as well as demonstrate that neuregulin activation of ErbB4 receptor to repress astrogenesis is mediated mainly though PARP-1 which contributes to astrocyte repression and decreased astrogenesis. These findings provide insight into how neural stem cells function and differentiate. Ko, Hui Ling, and Ee Chee Ren. “Functional Aspects of PARP1 in DNA Repair and Transcription.†Biomolecules, U.S. National Library of Medicine, 12 Nov. 2012, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030864/.
