The Vip1 inositol polyphosphate kinase family regulates polarized growth and modulates the microtubule cytoskeleton in fungi

PLoS Genet. 2014 Sep 25;10(9):e1004586. doi: 10.1371/journal.pgen.1004586. eCollection 2014 Sep.


Microtubules (MTs) are pivotal for numerous eukaryotic processes ranging from cellular morphogenesis, chromosome segregation to intracellular transport. Execution of these tasks requires intricate regulation of MT dynamics. Here, we identify a new regulator of the Schizosaccharomyces pombe MT cytoskeleton: Asp1, a member of the highly conserved Vip1 inositol polyphosphate kinase family. Inositol pyrophosphates generated by Asp1 modulate MT dynamic parameters independent of the central +TIP EB1 and in a dose-dependent and cellular-context-dependent manner. Importantly, our analysis of the in vitro kinase activities of various S. pombe Asp1 variants demonstrated that the C-terminal phosphatase-like domain of the dual domain Vip1 protein negatively affects the inositol pyrophosphate output of the N-terminal kinase domain. These data suggest that the former domain has phosphatase activity. Remarkably, Vip1 regulation of the MT cytoskeleton is a conserved feature, as Vip1-like proteins of the filamentous ascomycete Aspergillus nidulans and the distantly related pathogenic basidiomycete Ustilago maydis also affect the MT cytoskeleton in these organisms. Consistent with the role of interphase MTs in growth zone selection/maintenance, all 3 fungal systems show aspects of aberrant cell morphogenesis. Thus, for the first time we have identified a conserved biological process for inositol pyrophosphates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Fungal Proteins / metabolism
  • Fungi / genetics
  • Fungi / growth & development
  • Fungi / metabolism*
  • Inositol Phosphates / metabolism
  • Interphase
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / metabolism*
  • Phosphotransferases (Phosphate Group Acceptor) / metabolism*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / growth & development
  • Schizosaccharomyces / metabolism


  • Fungal Proteins
  • Inositol Phosphates
  • Microtubule-Associated Proteins
  • Phosphotransferases (Phosphate Group Acceptor)
  • inositol hexakisphosphate kinase

Grant support

This work was supported by the Deutsche Forschungsgemeinschaft ( project SFB590 (UF) and project FOR1334 (UF, MF, RF, NT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.