Biomedical Sciences ETDs

Publication Date

Fall 12-15-2023

Abstract

FcεRI is the ITAM receptor primarily responsible for the allergic response and immune hypersensitivity diseases such as asthma. Regulation of the strength of both FcεRI signaling, and the resulting outcomes, is accomplished via a complex array of molecular mechanisms whose interactions remain unclear. Here, I explored how the biophysical properties of antigens, crosstalk between FcεRI and integrin signaling and Arf6-mediated control of trafficking and exocytosis tune mast cell outcomes. I first found significant differences in FcεRI aggregation, phosphorylation and granule secretion after crosslinking with the multivalent antigen DNP-BSA or the small, trivalent antigen DF3. I also revealed a bi-directional, Syk-mediated crosstalk pathway between FcεRI and integrin β1/7 signaling. Last, I showed that the GTPase Arf6 influences mast cell degranulation, calcium signaling and both receptor and granule exocytosis. The findings here not only deepen the understanding of mast cell signaling, but provide insights into the molecular mechanisms of ITAM receptor activation.

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Diane S. Lidke, PhD

Second Committee Member

Jennifer M. Gillette, PhD

Third Committee Member

Tione Buranda, PhD

Fourth Committee Member

Michelle Ozbun, PhD

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