Actin's role in signaling light-induced phase shifts in the mammalian circadian clock
type: CreativeWork
description: The actin cytoskeleton is a critical part of intracellular structure, responsible for the general shape and integrity of all cells. New insights into the dynamic nature of the cytoskeleton describe additional roles for actin, including synaptic plasticity in the hippocampus, regulation of hormone release in endocrine cells, and as a signaling component involved in transcription. My research focused on the hypothesis that changes in actin state contribute to light-induced changes in the state of the circadian clock in the mammalian brain. In early night, the cells of the mammalian circadian clock, in the SCN, initiate a series of signaling events to translate environmental light into transcriptional changes which induce a delay of clock state. This signaling pathway, mediated by glutamate, involves activation of NMDA receptors, nitric oxide synthesis, and opening of ryanodine receptors with subsequent influx of calcium from intracellular stores. Activation of this cascade results in up-regulation of the clock genes, Period 1 and Period 2. This induction is mediated in part via CRE elements, through activation of the transcription factor, CREB. Connecting upstream signaling processes with the end result of transcriptional changes was a target of this study. Based on responses to glutamate in vitro, I hypothesized that activation of the early night light signaling pathway results in a rapid and transient decrease in actin polymerization, which is required for the phase delay to occur. I first characterized actin state around a day-night cycle, in order to determine whether sensitivity to actin depolymerization changes over this period. To this end, I showed that polymerized actin peaks in early night, but this oscillation in actin state is abolished in mice rendered genetically arrhythmic, the BMAL1 -/- mice. Secondly, I measured actin state after light exposure, and found that brief light pulses induced a breakdown of polymerized actin. By injecting the actin-stabiliz…
abstract: The actin cytoskeleton is a critical part of intracellular structure, responsible for the general shape and integrity of all cells. New insights into the dynamic nature of the cytoskeleton describe additional roles for actin, including synaptic plasticity in the hippocampus, regulation of hormone release in endocrine cells, and as a signaling component involved in transcription. My research focused on the hypothesis that changes in actin state contribute to light-induced changes in the state of the circadian clock in the mammalian brain. In early night, the cells of the mammalian circadian clock, in the SCN, initiate a series of signaling events to translate environmental light into transcriptional changes which induce a delay of clock state. This signaling pathway, mediated by glutamate, involves activation of NMDA receptors, nitric oxide synthesis, and opening of ryanodine receptors with subsequent influx of calcium from intracellular stores. Activation of this cascade results in up-regulation of the clock genes, Period 1 and Period 2. This induction is mediated in part via CRE elements, through activation of the transcription factor, CREB. Connecting upstream signaling processes with the end result of transcriptional changes was a target of this study. Based on responses to glutamate in vitro, I hypothesized that activation of the early night light signaling pathway results in a rapid and transient decrease in actin polymerization, which is required for the phase delay to occur. I first characterized actin state around a day-night cycle, in order to determine whether sensitivity to actin depolymerization changes over this period. To this end, I showed that polymerized actin peaks in early night, but this oscillation in actin state is abolished in mice rendered genetically arrhythmic, the BMAL1 -/- mice. Secondly, I measured actin state after light exposure, and found that brief light pulses induced a breakdown of polymerized actin. By injecting the actin-stabiliz…
author: Arnold, Jennifer
language: en
keywords: circadian, Actin, light
date published: 2013-02-03T19:17:20Z
date modified: 2026-07-22T22:25:31Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/42146