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CC BY-NC-ND V4.0, Open Access
Journal article
A Conserved Circadian Function for the Neurofibromatosis 1 Gene
Cell reports (Cambridge), Vol.22(13), pp.3416-3426
03/27/2018
PMID: 29590612
Abstract
Loss of the Neurofibromatosis 1 (Nf1) protein, neuro-fibromin, in Drosophila disrupts circadian rhythms of locomotor activity without impairing central clock function, suggesting effects downstream of the clock. However, the relevant cellular mechanisms are not known. Leveraging the discovery of output circuits for locomotor rhythms, we dissected cellular actions of neurofibromin in recently identified substrates. Herein, we show that neurofibromin affects the levels and cycling of calciumin multiple circadian peptidergic neurons. A prominent site of action is the pars intercerebralis (PI), the fly equivalent of the hypothalamus, with cell-autonomous effects of Nf1 in PI cells that secrete DH44. Nf1 interacts genetically with peptide signaling to affect circadian behavior. We extended these studies to mammals to demonstrate that mouse astrocytes exhibit a 24-hr rhythm of calcium levels, which is also attenuated by lack of neurofibromin. These findings establish a conserved role for neurofibromin in intracellular signaling rhythms within the nervous system.
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Details
- Title
- A Conserved Circadian Function for the Neurofibromatosis 1 Gene
- Creators
- Lei Bai - Howard Hughes Medical InstituteYool Lee - Washington State University, Biomedical Sciences, Department ofCynthia T. Hsu - Howard Hughes Medical InstituteJulie A. Williams - Howard Hughes Medical InstituteDaniel Cavanaugh - Howard Hughes Medical InstituteXiangzhong Zheng - Howard Hughes Medical InstituteCarly Stein - Howard Hughes Medical InstitutePaula Haynes - Howard Hughes Medical InstituteHan Wang - Howard Hughes Medical InstituteDavid H. Gutmann - Howard Hughes Medical InstituteAmita Sehgal - University of Pennsylvania
- Publication Details
- Cell reports (Cambridge), Vol.22(13), pp.3416-3426
- Academic Unit
- Elson S. Floyd College of Medicine
- Publisher
- Elsevier
- Number of pages
- 11
- Grant note
- 1-R35-NS097211-01 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R35NS097211 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01CA214146 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Identifiers
- 99901132535601842
- Language
- English
- Resource Type
- Journal article