Klaire Schott
Research Mentor: Not Available Not Available
Mentor Department: Not Available, Not Available
Author(s): Not Available
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 1
Abstract
Susceptibility to opioid addiction and overdose varies between individuals and contributes to
thousands of deaths annually in the United States, including 53,336 in 2024 (CDC 2024). These
differences in opioid response are likely influenced by genetic variation, including
polymorphisms in the μ-opioid receptor gene (OPRM1), which encodes MOR, a
G-protein-coupled receptor that mediates the effect of opioid drugs. In humans, a common single
nucleotide polymorphism (SNP) at position 118 (A118G) results in a glycine substitution for
alanine and has been associated with altered opioid sensitivity and tolerance. This causes an
asparagine to aspartic acid switch leading to the removal of an N-glycosylation site. Glycans
often act as trafficking signals, and their removal can cause receptor misfolding, retention in the
endoplasmic reticulum (ER), and decreased membrane expression, ultimately impairing ligand
binding and function. We hypothesize that A118G variant could modify the normal trafficking of
MOR. We utilized the analogous mouse variant, A112G, in cell culture, to investigate how this
genetic variation may influence MOR trafficking, internalization, and recycling at the cellular
and molecular level. While prior studies into the A118G variant have largely examined
differences in receptor expression and signaling, few have directly visualized MOR trafficking
dynamics. Using fluorescence microscopy to visualize Flag labeled MOR in PC12 cells, we
assess variant-specific differences in MOR internalization and recycling, providing mechanistic
insights into how A118G mutation may alter receptor regulation at the cellular level. Analyzing
the images via Fiji Image J, the results showed significant differences in constitutive
internalization between the WT FlagMOR and the A112G FlagMOR variant. We have seen some
differences in agonist mediated internalization and recycling, but we need to conduct further
studies. Our preliminary results suggest there are differences in trafficking dynamics in the
A112G FlagMOR variant that may contribute to previously observed differences in opioid
sensitivity and receptor regulation in patients.
