Date of Graduation

Fall 2020

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Randi Ulbricht

Keywords

CAPS1, RNA editing, secretion, stimulated secretion, GSIS, INS-1 cells

Subject Categories

Molecular Biology

Abstract

Calcium-dependent activator protein for secretion 1 (CAPS1) is involved in synaptic vesicle and large dense core vesicle fusion by bridging vesicles and the plasma membrane prior to vesicle fusion and cargo release. CAPS1 is subject to a post-transcriptional modification called RNA editing. RNA editing recodes a single amino acid in the region of the protein that interacts with the vesicle. This recoding event within CAPS1 has cellular consequences in neurons where edited CAPS1 overexpression increases basal secretion from neural synaptic vesicles. Our goal was to investigate how RNA editing within CAPS1 affects large dense core vesicle secretion in an insulinoma cell type that secretes insulin. We modified CAPS1 editing frequency within insulin-secreting cells, then measured non-stimulated and glucose stimulated secretion. We found cells with increased non-edited CAPS1 had less basal secretion compared to normal insulin-secreting cells, but edited CAPS1 did not affect secretion. Our study provides insight into how even slight modifications of CAPS1 RNA editing frequency could have profound effects on cellular secretion, which may suggest that CAPS1 editing is paramount to regulating cellular processes like neurotransmission and glucose homeostasis.

Copyright

© Kaylee M. Mathiason

Open Access

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