RRC ID 53905
Author Pascual-Ortiz M, Saiardi A, Walla E, Jakopec V, Künzel NA, Span I, Vangala A, Fleig U.
Title Asp1 Bifunctional Activity Modulates Spindle Function via Controlling Cellular Inositol Pyrophosphate Levels in Schizosaccharomyces pombe.
Journal Mol Cell Biol
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.
Volume 38(9)
Published 2018-5-1
DOI 10.1128/MCB.00047-18
PII MCB.00047-18
PMID 29440310
PMC PMC5902593
MeSH Chromosome Segregation / physiology Cytoskeletal Proteins / metabolism* Cytoskeletal Proteins / physiology* Inositol Inositol Phosphates / metabolism Inositol Phosphates / physiology Kinesin / metabolism Microtubule-Associated Proteins Microtubules Mitosis / physiology Phosphotransferases (Phosphate Group Acceptor) / metabolism Schizosaccharomyces Schizosaccharomyces pombe Proteins / metabolism* Schizosaccharomyces pombe Proteins / physiology* Spindle Apparatus / metabolism* Spindle Apparatus / physiology Sulfite Reductase (NADPH) / metabolism
IF 3.611
Times Cited 5
Yeast FY8347 FY17673 FY18583