Mechanisms of Melanopsin Photoresponse Termination: Biochemical Analysis of the Intrinsically Photosensitive Retinal Ganglion Cell Photopigment

Frederick, Courtney

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Year:: 2013
Contributor:: Frederick, Courtney (creator); BERSON, DAVID (Director); ZIMMERMAN, ANITA (Reader); MARSHALL, JOHN (Reader); BARNEA, GILAD (Reader); WESSEL, GARY (Reader); Brown University. BIOMED: Molecular Pharmacology, Physiology, and Biotechnology (sponsor)
Genre:: theses
Subject:: melanopsin; phototransduction; intrinsically photosensitive retinal ganglion cells
Extent:: xvii, 178 p.
DOI: https://doi.org/10.7301/Z0N014WN

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Abstract:: Abstract of Mechanisms of Melanopsin Photoresponse Termination: Biochemical Analysis of the Intrinsically Photosensitive Retinal Ganglion Cell Photopigment, by Courtney E. Frederick, Ph.D., Brown University, May 2014 Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of unique photoreceptors in the vertebrate retina that mediate a number of physiologic responses to light such as circadian entrainment, melatonin release, and the pupillary light reflex. They are characterized by a depolarizing light response that is sluggish in the absence of synaptic influence and a slow recovery in the dark. The distinctive photoreceptive properties exhibited by ipRGCs are attributed to the activity of the G-protein coupled receptor (GPCR) melanopsin, which is endogenously expressed in these cells. Although many details of melanopsin signaling have been established, little has been presented regarding termination of the pathway. This study is an examination of the termination of the phototransduction cascade initiated by the melanopsin. Whole cell patch recordings made on HEK293 cells expressing C-terminally truncated mouse melanopsin revealed photocurrents that failed to terminate. Likewise, a mouse melanopsin protein whose putative phosphorylation sites were neutralized by alanine substitution also generated persistent photoresponses that did not recover. Reverse transcriptase polymerase chain reaction (RT-PCR) done on single melanopsin positive rat retinal ganglion cells revealed the presence of both β arrestin -1 and -2 transcripts. Immunohistochemical staining on mouse and rat vertical sections confirmed the expression of both β arrestin protein isoforms in melanopsin immunopositive retinal ganglion cells while excluding the presence of rod and cone arrestin. The termination of phototransduction at the GPCR level typically occurs when the C-terminal tail of the photopigment is phosphorylated and subsequently bound by an isoform of arrestin. The data collected here suggests a canonical mechanism of C-terminal tail regulation and the involvement of an isoform of β arrestin in the melanopsin signaling pathway.
Notes:: Thesis (Ph.D. -- Brown University (2013)

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Frederick, Courtney, "Mechanisms of Melanopsin Photoresponse Termination: Biochemical Analysis of the Intrinsically Photosensitive Retinal Ganglion Cell Photopigment" (2013). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0N014WN

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Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations

Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department.
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