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The mitogen-activated protein kinase (MAPK) pathway: a signaling conduit for photic entrainment of the central mammalian circadian clock

Butcher, Gregory Quinn
http://rave.ohiolink.edu/etdc/view?acc_num=osu1147206998

Abstract Details

2006, Doctor of Philosophy, Ohio State University, Neuroscience.
The central biological clock, located in suprachiasmatic nuclei (SCN) of the hypothalamus in mammals, coordinates physiological and behavioral processes to an approximate 24 hr (circadian) rhythm. The endogenous timing mechanism remains synchronized to the exogenous environment through the influence of timing cues (zeitgebers), such as light via a process known as entrainment. The studies presented here describe the functional and mechanistic assessment of the p42/44 mitogen-activated protein kinase (MAPK) cascade as a putative input pathway to the SCN. The following hypotheses are tested using a variety of behavioral, cellular, and biochemical techniques. 1) Light-induced behavioral phase shifting in mice is coupled via a MAPK dependent mechanism. 2) Light activation of the MAPK pathway is stringently regulated with respect to the time course of activation / inactivation and subcellular localization of ERK within neurons. 3) Light-induced phosphorylation of p90 ribosomal S6 kinases (RSKs) within the SCN is phase restricted to the subjective night and is dependent upon activation of the MAPK pathway. 4) Light-induced phosphorylation of mitogen- and stress-activated kinases (MSKs) within the SCN is dependent on a signaling cassette consisting of the neuromodulator pituitary adenylate cyclase activating polypeptide (PACAP) and the MAPK pathway. 5) Light-induced phase advances, but not phase delays, are attenuated in mice lacking MSKs. Conversely, light-induced phase delays, but not phase advances, are attenuated in mice lacking RSKs. The data presented herein demonstrate that functional coupling between photic stimuli and behavioral phase shifting occurs via a MAPK signaling pathway. Furthermore, expression profiles for maximal light-induced activation of two MAPK substrates, RSK1 and MSK1, suggest that these kinases may occupy divergent functional roles within the entrainment mechanism. Preliminary data testing this possibility indicates that RSK and MSK signalling may function in a partially compensatory and complimentary manner rather than exclusively distinct pathways.
Karl Obrietan (Advisor)
196 p.
MAPK; circadian; entrainment; RSK; MSK; SCN

Recommended Citations

Citations

  • Butcher, G. Q. (2006). The mitogen-activated protein kinase (MAPK) pathway: a signaling conduit for photic entrainment of the central mammalian circadian clock [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1147206998

    APA Style (7th edition)

  • Butcher, Gregory. The mitogen-activated protein kinase (MAPK) pathway: a signaling conduit for photic entrainment of the central mammalian circadian clock. 2006. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1147206998.

    MLA Style (8th edition)

  • Butcher, Gregory. "The mitogen-activated protein kinase (MAPK) pathway: a signaling conduit for photic entrainment of the central mammalian circadian clock." Doctoral dissertation, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1147206998

    Chicago Manual of Style (17th edition)

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© 2006, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.