Brady Braund
Pronouns: he/him
Research Mentor(s): You Lu
Research Mentor School/College/Department: Molecular and Integrative Physiology / Medicine
Program: UROP
Session: Session 7 (4:40pm – 5:30pm)
Authors: You Lu, Brady Braund
Abstract
Kidney proximal tubules play an important role in the overall function of the kidney and its ability to properly filtrate substances and reabsorb nutrients. Much of the reabsorption function in proximal tubules is fulfilled by a wide array of cell surface localized transporters. Many newly synthesized transporters require complex folding in the endoplasmic reticulum (ER) before trafficking to the cell surface and are subject to quality control by ER-associated degradation (ERAD). So far, the importance of SEL1L-HRD1 ERAD is largely unexplored in kidney proximal tubules. The focus of this study is to examine the physiological consequences of conditional ablation of Sel1L specifically in proximal tubules and to identify potential ERAD substrates. We verified that Sel1L was successfully deleted in the proximal tubules using the Pepck-promoter-driven Cre recombinase expression. We hypothesize sodium-glucose co-transporter 2 (SGLT2) may be an ERAD substrate, due to the fact that it is N-glycosylated, a key feature shared by many known ERAD substrates. Future experiments are required to discover if there is any difference in SGLT2 protein size and abundance of SGLT2 when comparing wild-type and Sel1L knockout mice, eventually revealing if SGLT2 is an ERAD substrate. An in-depth understanding of whether SGLT2 is quality controlled by SEL1L-HRD1 ERAD could provide valuable insights into the pathogenesis of certain kidney disorders, thereby facilitating a better comprehension of the underlying mechanisms and potential therapeutic interventions.
