The inositol 1,3,4,5,6-pentakisphosphate (IP5) 2-kinase (Ipk1) catalyzes production of inositol hexakisphosphate (IP6) in eukaryotic cells. Previous studies have shown that IP6 is required for efficient nuclear mRNA export in budding yeast Saccharomyces cerevisiae. Here, we report the first functional analysis of ipk1(+) in Schizosaccharomyces pombe (sp). The spIpk1 is unique amongst Ipk1 orthologues in that it harbors a novel amino (N)-terminal domain with coiled-coil structural motifs similar to BAR-domain proteins. Mutants with ipk1(+) deleted (ipk1Delta) had mRNA export defects, as well as pleiotropic defects in polarized growth, cell morphology, endocytosis, and cell separation. The spIpk1 catalytic carboxy-terminal domain was required to rescue these defects, and the mRNA export block was genetically linked to spDbp5 function and likely IP6 production. However, overexpression of the N-terminal domain alone also inhibited these functions in wild-type cells. This revealed a distinct non-catalytic function for the N-terminal domain. To test for connections with other inositol polyphosphates, we also analyzed whether loss of asp1(+) function, encoding an IP6 kinase downstream of Ipk1, had an effect on ipk1Delta cells. The asp1Delta mutant alone did not block mRNA export, and its cell morphology, polarized growth, and endocytosis defects were less severe than those in ipk1Delta cells. Moreover, ipk1Delta asp1Delta double mutants had altered inositol polyphosphate levels distinct from the ipk1Delta mutant. This suggested novel roles for asp1(+) upstream of ipk1(+). We propose that IP6 production is a key signaling linchpin for regulating multiple essential cellular processes.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|