Circadian rhythmicity mediated by temporal regulation of the activity of p38 MAPK

Abstract

Circadian clocks are composed of central oscillators, input pathways that transduce external information to the oscillators, and output pathways that allow the oscillators to temporally regulate cellular processes. Little is known about the output pathways. In this study, we show that the Neurospora crassa osmosensing MAPK pathway, essential for osmotic stress responses, is a circadian output pathway that regulates daily rhythms in the expression of downstream genes. Rhythmic activation of the highly conserved stress-activated p38-type MAPK [Osmotically Sensitive-2 (OS-2)] by the N. crassa circadian clock allows anticipation and preparation for hyperosmotic stress and desiccation that begin at sunrise. These results suggest a conserved role for MAPK pathways in circadian rhythmicity.circadian output pathway ͉ circadian rhythm ͉ Neurospora crassa ͉ osmotic stress phosphorelay

Circadian Activation of the Mitogen-Activated Protein Kinase MAK-1 Facilitates Rhythms in Clock-Controlled Genes in Neurospora crassa

“…These pathways are likely responsible for controlling both unique and overlapping cellular processes and stress responses that occur at various times in the day, consistent with our finding that not all ccg targets of the MAK-1 pathway behave arrhythmically in ⌬mak-1 cells: circadian rhythms in mRNA accumulation of 2 downstream targets of MAK-1, ccg-7 and NCU08949, were maintained in the ⌬mak-1 strain (data not shown). P-OS-2 peaks in the morning, at a time when the cell is beginning to encounter potential osmotic changes in the environment (22), while P-MAK-1 and P-MAK-2 peak later in the afternoon, at a time when the growth rate of the cells is increasing and conidiation is repressed (57). Interestingly, when MAK-1 was deleted, the levels of ccg-1 mRNA were greatly reduced.…”

“…In spite of this, low-amplitude ccg-1 mRNA rhythms were observed in the deletion strain, albeit with less reproducibility than in wild-type cells. We previously reported that ccg-1 rhythmicity depends upon a functional OS-2 pathway (22), and ccg-1 is induced in response to a variety of stresses (66)(67)(68)(69). Thus, it appears that both MAPK pathways contribute to robust rhythmicity in the expression of some target genes, including ccg-1.…”

“…Additionally, clock regulation of major signaling pathways, such as mitogen-activated protein kinase (MAPK) pathways, provides mechanisms for circadian regulation of large sets of functionally related downstream target genes of the pathway. For example, we previously found that the Neurospora FWO controls rhythmic activity of the osmolarity-sensitive (OS) MAPK pathway and downstream ccg targets of the pathway (20)(21)(22).…”

Mitogen-Activated Protein Kinase Cascade Required for Regulation of Development and Secondary Metabolism in Neurospora crassa

“…A twocomponent regulatory system that includes the histidine kinase OS-1 and the response regulator RRG-1 operates upstream of the OS-2 MAPK pathway (24). It has recently been shown that this MAPK cascade is an output pathway for the Neurospora circadian clock (56).…”

The Neurospora crassa DCC-1 Protein, a Putative Histidine Kinase, Is Required for Normal Sexual and Asexual Development and Carotenogenesis

“…The most obvious and prominent circadianly controlled rhythm in N. crassa is that of conidiation, which forms a characteristic conidial banding-pattern on plates or in long glass culture tubes (race tubes). Also, it has been previously reported that RRG-1 of N. crassa functions in an output pathway to regulate circadian rhythmicity, although the upstream HK was not identified (41). Because of the intimate association of the DCC-1 sensor HK with the process of conidiation and the involvement of a two-component system protein (RRG-1) in the regulation of rhythmicity (2), we asked whether DCC-1 also affects this process.…”