Protein phosphatase 2A cooperates with the autophagyrelated kinase UNC-51 to regulate axon guidance in Caenorhabditis elegans

Ken Ichi Ogura, Takako Okada, Shohei Mitani, Keiko Gengyo-Ando, David L. Baillie, Yuji Kohara, Yoshio Goshima

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

UNC-51 is a serine/threonine protein kinase conserved from yeast to humans. The yeast homolog Atg1 regulates autophagy (catabolic membrane trafficking) required for surviving starvation. In C. elegans, UNC-51 regulates the axon guidance of many neurons by a different mechanism than it and its homologs use for autophagy. UNC-51 regulates the subcellular localization (trafficking) of UNC-5, a receptor for the axon guidance molecule UNC-6/Netrin; however, the molecular details of the role for UNC-51 are largely unknown. Here, we report that UNC-51 physically interacts with LET-92, the catalytic subunit of serine/threonine protein phosphatase 2A (PP2A-C), which plays important roles in many cellular functions. A low allelic dose of LET-92 partially suppressed axon guidance defects of weak, but not severe, unc-51 mutants, and a low allelic dose of PP2A regulatory subunits A (PAA-1/PP2A-A) and B (SUR-6/PP2A-B) partially enhanced the weak unc-51 mutants. We also found that LET-92 can work cell-nonautonomously on axon guidance in neurons, and that LET-92 colocalized with UNC-51 in neurons. In addition, PP2A dephosphorylated phosphoproteins that had been phosphorylated by UNC-51. These results suggest that, by forming a complex, PP2A cooperates with UNC-51 to regulate axon guidance by regulating phosphorylation. This is the first report of a serine/threonine protein phosphatase functioning in axon guidance in vivo.

Original languageEnglish
Pages (from-to)1657-1667
Number of pages11
JournalDevelopment
Volume137
Issue number10
DOIs
Publication statusPublished - 2010 May 15

Keywords

  • Axon guidance
  • C. Elegans
  • PP2A
  • Serine/threonine protein kinase
  • Serine/threonine protein phosphatase

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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