期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 32, 页码 E6669-E6677出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1620483114
关键词
SIK3; HDAC4; male sex drive rhythm; circadian rhythms; Drosophila
资金
- National Institute on Deafness and Other Communication Disorders [R01DC0113967]
- National Institute of General Medical Sciences (NIGMS) [R01GMDC05606]
- Maximizing Investigators' Research Award from NIGMS [(R35) GM1180875]
- Cancer Research UK
- Versus Arthritis [18475] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10139, NF-SI-0508-10299, RC-PG-0407-10054] Funding Source: researchfish
- Versus Arthritis [20639] Funding Source: researchfish
The physiology and behavior of many organisms are subject to daily cycles. In Drosophila melanogaster the daily locomotion patterns of single flies are characterized by bursts of activity at dawn and dusk. Two distinct clusters of clock neurons-morning oscillators (M cells) and evening oscillators (E cells)-are largely responsible for these activity bursts. In contrast, male-female pairs of flies follow a distinct pattern, most notably characterized by an activity trough at dusk followed by a high level of male courtship during the night. This male sex drive rhythm (MSDR) is mediated by the M cells along with DN1 neurons, a cluster of clock neurons located in the dorsal posterior region of the brain. Here we report that males lacking Salt-inducible kinase 3 (SIK3) expression in M cells exhibit a short period of MSDR but a long period of single-fly locomotor rhythm (SLR). Moreover, lack of Sik3 in M cells decreases the amplitude of PERIOD (PER) cycling in DN1 neurons, suggesting that SIK3 non-cell-autonomously regulates DN1 neurons' molecular clock. We also show that Sik3 reduction interferes with circadian nucleocytoplasmic shuttling of Histone deacetylase 4 (HDAC4), a SIK3 phosphorylation target, in clock neurons and that constitutive HDAC4 localization in the nucleus shortens the period ofMSDR. Taking these findings together, we conclude that SIK3-HDAC4 signaling in M cells regulates MSDR by regulating the molecular oscillation in DN1 neurons.
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