Title

Modulation of Allosteric Regulation of Muscarinic Signaling by Chemical Modification of the Receptor

Presenter Information

Dana Lawson

Department

Biological Sciences

Major

Biological Sciences

Research Advisor

Aronstam, Robert

Advisor's Department

Biological Sciences

Funding Source

OURE

Abstract

M1 muscarinic acetylcholine receptors are G protein-coupled receptors involved with functions such as learning and memory. Learning about these receptors is beneficial so that pathways involved with diseases such as Alzheimer’s can be better understood. Deep within the receptor is the active site where acetylcholine binds, while the allosteric site is above it. Between two loops on this allosteric site is a disulfide bond. Using CHO cells expressing M1 receptors, we explored the role that this disulfide bond has on the acetylcholine response by breaking it with dithiothreitol (DTT). The acetylcholine response (which triggers a Ca2+ release from the endoplasmic reticulum into the cytosol) of this experimental group was compared to that of unmodified cells. This response was measured as a function of cytosolic Ca2+ concentrations using a Ca2+ imaging assay. In preliminary experiments, DTT increased this response, suggesting that the disulfide bond may block access to the active site.

Biography

Dana has enjoyed her research experience working in Dr. Aronstam’s Laboratory of Neurobiology, and is excited to participate in this year’s Undergraduate Research Conference. Her training in calcium imaging, CHO cell culture, and the Ca2+ signaling pathway has been very rewarding. She also enjoys participating in the Phi Sigma Biological Honor Society as well as the Alpha Chi Sigma Professional Chemistry Fraternity. She will be graduating in December 2015 with minors in Chemistry and Psychology, and plans to pursue a career in biological research.

Research Category

Sciences

Presentation Type

Poster Presentation

Document Type

Poster

Location

Upper Atrium/Hall

Presentation Date

15 Apr 2015, 9:00 am - 11:45 am

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Apr 15th, 9:00 AM Apr 15th, 11:45 AM

Modulation of Allosteric Regulation of Muscarinic Signaling by Chemical Modification of the Receptor

Upper Atrium/Hall

M1 muscarinic acetylcholine receptors are G protein-coupled receptors involved with functions such as learning and memory. Learning about these receptors is beneficial so that pathways involved with diseases such as Alzheimer’s can be better understood. Deep within the receptor is the active site where acetylcholine binds, while the allosteric site is above it. Between two loops on this allosteric site is a disulfide bond. Using CHO cells expressing M1 receptors, we explored the role that this disulfide bond has on the acetylcholine response by breaking it with dithiothreitol (DTT). The acetylcholine response (which triggers a Ca2+ release from the endoplasmic reticulum into the cytosol) of this experimental group was compared to that of unmodified cells. This response was measured as a function of cytosolic Ca2+ concentrations using a Ca2+ imaging assay. In preliminary experiments, DTT increased this response, suggesting that the disulfide bond may block access to the active site.