Anna Chiara Russo
Pronouns: She/Her
Research Mentor(s): Rachel Reinert
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine/MEND / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 1 – 10am – 10:50am
Room: League Ballroom
Authors: Anna Chiara Russo, Rohit Ray , Rachel Reinert
Presenter: 111
Abstract
Endoplasmic reticulum associated degradation (ERAD) is a primary mechanism of cellular protein quality control that is critical to maintain function of many endocrine cell types. ERAD targets misfolded ER proteins for proteasomal degradation through two highly conserved proteins: Hrd1, which ubiquitinates ER proteins for degradation, and Sel1L, an adaptor protein required for substrate recognition and ERAD function. Pancreatic islet alpha cells synthesize and secrete glucagon, an important hormone in glucose regulation – but little is known about protein quality control in alpha cell function. To investigate the role of ERAD in alpha cells, we targeted deletion of Sel1L in glucagon-expressing cells using the Cre-lox system in mice. Alpha cell Sel1L knockout (GKO) mice showed normal growth and glucose homeostasis but had impaired glucagon secretion in response to hypoglycemia. Pancreatic glucagon levels were also decreased in GKO mice. We thus used immunohistochemistry to explore the cause for reduced glucagon production in ERAD deficient alpha cells. Pancreatic alpha cell mass, as detected by glucagon immunolabeling, was decreased by 37% in GKO mice, reflecting reduced alpha number. The percentage of alpha cells labeled with the TUNEL apoptosis marker was unchanged in GKO alpha cells compared to littermate controls, suggesting that ERAD deficiency does not significantly affect alpha cell death. We are now quantifying alpha cell proliferation by labeling with the nuclear marker Ki67. Collectively, these data suggest that ERAD is important to maintain a functional alpha cell population by controlling alpha cell number and glucagon expression. These findings reveal fundamental mechanisms in alpha cell biology and ultimately may help in developing therapies to better regulate blood glucose levels in diabetes.
Biomedical Sciences, Interdisciplinary
