Protein phosphatase 2A cooperates with the autophagy-related kinase UNC-51 to regulate axon guidance in Caenorhabditis elegans.
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-non-autonomously 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.
Ogura
Ken-ichi
K
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. kenogura@med.yokohama-cu.ac.jp
Okada
Takako
T
Mitani
Shohei
S
Gengyo-Ando
Keiko
K
Baillie
David L
DL
Kohara
Yuji
Y
Goshima
Yoshio
Y
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D001370:Axonal Transport / Q000235:genetics / Q000502:physiology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D021122:Protein Subunits; D011494:Protein Kinases; C112443:UNC-51 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2
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