Cell division defects of Schizosaccharomyces pombe liz1- mutants are caused by defects in pantothenate uptake.
The liz1+ gene of the fission yeast Schizosaccharomyces pombe was previously identified by complementation of a mutation that causes abnormal mitosis when ribonucleotide reductase is inhibited. Liz1 has similarity to transport proteins from Saccharomyces cerevisiae, but the potential substrate and its connection to the cell division cycle remain elusive. We report here that liz1+ encodes a plasma membrane-localized active transport protein for the vitamin pantothenate, the precursor of coenzyme A (CoA). Liz1 is required for pantothenate uptake at low extracellular concentrations. A lack of pantothenate uptake results in three phenotypes: (i) slow growth, (ii) delayed septation, and (iii) aberrant mitosis in the presence of hydroxyurea (HU). All three phenotypes are suppressed by high extracellular concentrations of pantothenate, where pantothenate uptake occurs by passive diffusion. liz1Delta mutants are viable because they can synthesize pantothenate from uracil as an endogenous source. The use of uracil for both pantothenate biosynthesis and deoxyribonucleotide generation provides an explanation for the aberrant mitosis in the presence of HU. HU blocks ribonucleotide reductase, and we propose that the accumulation of ribonucleotides reduces uracil biosynthesis by feedback inhibition of aspartate transcarbamoylase. Thus, the addition of HU to liz1Delta mutants results in a shortage of pantothenate. Because liz1Delta mutants show striking similarities to mutants with defects in fatty acid biosynthesis, we propose that the shortage of pantothenate compromises fatty acid synthesis, resulting in slow growth and mitotic defects.
Stolz
Jürgen
J
Department of Cell Biology and Plant Physiology, Universität Regensburg, Germany. juergen.stolz@biologie.uni-regensburg.de
Caspari
Thomas
T
Carr
Antony M
AM
Sauer
Norbert
N
D002455:Cell Division; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010205:Pantothenic Acid / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D012568:Schizosaccharomyces / Q000254:growth & development* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014498:Uracil / Q000378:metabolism; D015091:beta-Alanine / Q000378:metabolism
D005656:Fungal Proteins; C493835:Liz1 protein, S pombe; D026901:Membrane Transport Proteins; D011422:Propionates; D029702:Schizosaccharomyces pombe Proteins; D015091:beta-Alanine; D010205:Pantothenic Acid; D014498:Uracil