Asp1 bifunctional activity modulates spindle function via controlling cellular inositol pyrophosphate levels in Schizosaccharomyces pombe

Pascual-Ortiz M, Saiardi A, Walla E, Jakopec V, Kuenzel NA, Span I, Vangala A, Fleig U (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Molecular and Cellular Biology American Society for Microbiology

Book Volume: 38

Article Number: e00047-18

Journal Issue: 9

DOI: 10.1128/MCB.00047-18

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.

Authors with CRIS profile

Ingrid Span

Involved external institutions

Heinrich-Heine-Universität Düsseldorf DE Germany (DE) University College London (UCL) GB United Kingdom (GB)

How to cite

APA:

Pascual-Ortiz, M., Saiardi, A., Walla, E., Jakopec, V., Kuenzel, N.A., Span, I.,... Fleig, U. (2018). Asp1 bifunctional activity modulates spindle function via controlling cellular inositol pyrophosphate levels in Schizosaccharomyces pombe. Molecular and Cellular Biology, 38(9). https://doi.org/10.1128/MCB.00047-18

MLA:

Pascual-Ortiz, Marina, et al. "Asp1 bifunctional activity modulates spindle function via controlling cellular inositol pyrophosphate levels in Schizosaccharomyces pombe." Molecular and Cellular Biology 38.9 (2018).

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