Determinants of β-arrestin2 Recruitment into Primary Cilia
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. School of Biomedical Science Honors Theses; 2015
Primary cilia are specialized organelles found on nearly every cell type in the human body. They perform specialized sensory and signaling functions, and are required for cellular homeostasis and proper development. Despite the fact that defects in primary cilia formation and function have been implicated in numerous diseases, the precise functions of primary cilia on most cell types are unknown. Primary cilia are known to coordinate signal transduction pathways, including G protein-coupled receptor (GPCR) signaling. However, little is known about the regulation of cilia-mediated GPCR signaling. β-arrestins are important regulators of GPCR signaling at the plasma membrane and act to terminate or facilitate GPCR signaling. Two different β-arrestin isoforms, β-arrestin1 (βarr1) and β-arrestin2 (βarr2), are expressed ubiquitously and regulate most GPCRs in a fairly nonspecific manner. Yet, we have discovered that agonist treatment initiates recruitment of βarr2, but not βarr1, into the ciliary compartment. We hypothesize that a specific domain(s) found in βarr2, mediates its recruitment into primary cilia following the activation of ciliary GPCRs. In order to identify the domain(s) mediating the recruitment of βarr2 into primary cilia, we used overlap extension PCR to generate chimeric proteins containing domains of βarr1 and βarr2. Our results indicate that two distinct domains within βarr2 are mediating its recruitment into the primary cilium following treatment with SST. Understanding the molecular basis of βarr2 recruitment into the primary cilium is a vital step to understanding the mechanism of ciliary GPCR signaling and its role in ciliary disorders.
Academic Major: Biomedical Science
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