title: Circadian activation of the mitogen-activated protein kinase MAK-1 facilitates rhythms in clock-controlled genes in Neurospora crassa.
abstract: The circadian clock regulates the expression of many genes involved in a wide range of biological functions through output pathways such as mitogen-activated protein kinase (MAPK) pathways. We demonstrate here that the clock regulates the phosphorylation, and thus activation, of the MAPKs MAK-1 and MAK-2 in the filamentous fungus Neurospora crassa. In this study, we identified genetic targets of the MAK-1 pathway, which is homologous to the cell wall integrity pathway in Saccharomyces cerevisiae and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in mammals. When MAK-1 was deleted from Neurospora cells, vegetative growth was reduced and the transcript levels for over 500 genes were affected, with significant enrichment for genes involved in protein synthesis, biogenesis of cellular components, metabolism, energy production, and transcription. Additionally, of the ~500 genes affected by the disruption of MAK-1, more than 25% were previously identified as putative clock-controlled genes. We show that MAK-1 is necessary for robust rhythms of two morning-specific genes, i.e., ccg-1 and the mitochondrial phosphate carrier protein gene NCU07465. Additionally, we show clock regulation of a predicted chitin synthase gene, NCU04352, whose rhythmic accumulation is also dependent upon MAK-1. Together, these data establish a role for the MAK-1 pathway as an output pathway of the circadian clock and suggest a link between rhythmic MAK-1 activity and circadian control of cellular growth.
authors.affiliation: Department of Biology, Texas A&M University, College Station, Texas, USA.
authors.forename: Lindsay D
authors.initials: LD
authors.lastname: Bennett
authors.forename: Phillip
authors.initials: P
authors.lastname: Beremand
authors.forename: Terry L
authors.initials: TL
authors.lastname: Thomas
authors.forename: Deborah
authors.initials: D
authors.lastname: Bell-Pedersen
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002687:Chitin Synthase / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009492:Neurospora crassa / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059467:Transcriptome
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D002687:Chitin Synthase; D020928:Mitogen-Activated Protein Kinases