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Mol Cell Biol. 2018 Apr 16;38(9). pii: e00047-18. doi: 10.1128/MCB.00047-18. Print 2018 May 1.

Asp1 Bifunctional Activity Modulates Spindle Function via Controlling Cellular Inositol Pyrophosphate Levels in Schizosaccharomyces pombe.

Author information

1
Eukaryotische Mikrobiologie, Institut für Funktionelle Genomforschung der Mikroorganismen, Heinrich Heine Universität, Düsseldorf, Germany.
2
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
3
Institut für Physikalische Biologie, Heinrich Heine Universität, Düsseldorf, Germany.
4
Eukaryotische Mikrobiologie, Institut für Funktionelle Genomforschung der Mikroorganismen, Heinrich Heine Universität, Düsseldorf, Germany fleigu@hhu.de.

Abstract

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.

KEYWORDS:

PPIP5K family; Schizosaccharomyces pombe; chromosome segregation; inositol pyrophosphate; microtubule; mitosis; phosphatase; signaling molecules; yeast

PMID:
29440310
PMCID:
PMC5902593
DOI:
10.1128/MCB.00047-18
[Indexed for MEDLINE]
Free PMC Article

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