Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 38, Issue 9, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00047-18
Keywords
PPIP5K family; Schizosaccharomyces pombe; chromosome segregation; inositol pyrophosphate; microtubule; mitosis; phosphatase; signaling molecules; yeast
Categories
Funding
- Deutsche Forschungsgemeinschaft [FOR1334]
- Manchot Graduate school MOI II (Juergen Manchot Stiftung)
- Fonds der Chemischen Industrie
- Medical Research Council (MRC) [MC_UU_1201814]
- MRC [MC_U122680443, MC_UU_00012/4, MC_UU_12018/4] Funding Source: UKRI
- Medical Research Council [MC_UU_00012/4, MC_UU_12018/4, MC_U122680443] Funding Source: researchfish
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The generation of two daughter cells with the same genetic information requires error-free chromosome segregation during mitosis. Chromosome transmission fidelity is dependent on spindle structure/function, which requires Asp1 in the fission yeast Schizosaccharomyces pombe. Asp1 belongs to the diphosphoinositol pentakisphosphate kinase (PPIP5K)/Vip1 family which generates high-energy inositol pyrophosphate (IPP) molecules. Here, we show that Asp1 is a bifunctional enzyme in vivo: Asp1 kinase generates specific IPPs which are the substrates of the Asp1 pyrophosphatase. Intracellular levels of these IPPs directly correlate with microtubule stability: pyrophosphatase loss-of-function mutants raised Asp1-made IPP levels 2-fold, thus increasing microtubule stability, while overexpression of the pyrophosphatase decreased microtubule stability. Absence of Asp1-generated IPPs resulted in an aberrant, increased spindle association of the S. pombe kinesin-5 family member Cut7, which led to spindle collapse. Thus, chromosome transmission is controlled via intracellular IPP levels. Intriguingly, identification of the mitochondrion-associated Met10 protein as the first pyrophosphatase inhibitor revealed that IPPs also regulate mitochondrial distribution.
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