Kinesin-14 and Its Regulatory Partner Have Unique Functions in Candida albicans
Mitotic division, mating, and hypha formation in Candida albicans require the action of microtubules, motors, and a number of specialized regulatory proteins. The kinesin-14 motor CaKar3 is a prominent player in these processes. Frazer et al. (p. 755–774) show that unlike humans, Drosophila, and budding and fission yeasts, C. albicans expresses a single kinesin-like binding partner (dubbed CaCik1) that forms a heterodimer with CaKar3, regulating its localization and function. Loss of CaCik1 prevents nuclear fusion during mating, inhibits invasive hypha formation, and causes cell cycle arrest due to failure to establish spindle bipolarity. This last phenotype differs significantly from deletions of kinesin-14 motors in other species, suggesting that hundreds of millions of years of evolution have led to divergence in kinesin motor-driven processes in this human pathogen.
How To Cock the Trigger (If You Are a Ciliate)
Many ciliates synthesize secretory vesicles whose contents can be explosively released from cells upon stimulation. In Tetrahymena thermophila, the extrusion is driven by expansion of polypeptide-based springs that crystallize during secretory vesicle formation. Previous work on the crystal-forming units revealed that spring assembly required proteolytic processing, but neither the proteases involved nor the function of specific processing steps was known. By exploiting an extensive gene expression database, two key proteases have now been identified. Kumar et al.'s analysis (p. 817–833) of a cysteine cathepsin, CTH4, now reveals, surprisingly, that the secretory crystals, even after assembly, require refinement by a subtle processing step to be fully competent for expansion.
Exploring Genetic Redundancy at the Pathway Level
As a result of ancestral whole-genome and small-scale duplication events, eukaryotic genomes still contain a substantial fraction of duplicated genes. Metabolic pathways, and more particularly glycolysis, are specifically enriched for functionally redundant paralogs. Performing the simultaneous deletion of 13 of the 27 glycolytic paralogs in the model yeast Saccharomyces cerevisiae, Solis-Escalante et al. (p. 804–816) experimentally explore the role of genetic redundancy in the glycolytic pathway, a nearly ubiquitous catabolic highway for sugar utilization. The complete absence of a phenotypic response to these cumulative deletions, despite thorough characterization by combination of a quantitative systems approach and semiquantitative analysis in a wide array of growth environments, indicates that duplication of glycolytic genes is not a prerequisite for achieving the high glycolytic fluxes and fermentative capacities that are characteristic of S. cerevisiae. It also argues against gene dosage effects as a means of fixing minor glycolytic paralogs in the yeast genome. Furthermore, the constructed “minimal glycolysis” strain is an attractive test bed for mathematical modeling of glycolysis and provides an interesting, simplified starting point for laboratory studies on endogenous and heterologous glycolysis.