RAE-1, a novel PHR binding protein, is required for axon termination and synapse formation in Caenorhabditis elegans

J Neurosci. 2012 Feb 22;32(8):2628-36. doi: 10.1523/JNEUROSCI.2901-11.2012.

Abstract

Previous studies in Caenorhabditis elegans showed that RPM-1 (Regulator of Presynaptic Morphology-1) regulates axon termination and synapse formation. To understand the mechanism of how rpm-1 functions, we have used mass spectrometry to identify RPM-1 binding proteins, and have identified RAE-1 (RNA Export protein-1) as an evolutionarily conserved binding partner. We define a RAE-1 binding region in RPM-1, and show that this binding interaction is conserved and also occurs between Rae1 and the human ortholog of RPM-1 called Pam (protein associated with Myc). rae-1 loss of function causes similar axon and synapse defects, and synergizes genetically with two other RPM-1 binding proteins, GLO-4 and FSN-1. Further, we show that RAE-1 colocalizes with RPM-1 in neurons, and that rae-1 functions downstream of rpm-1. These studies establish a novel postmitotic function for rae-1 in neuronal development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Amino Acid Motifs / genetics
  • Amino Acid Sequence / genetics
  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • Gene Expression Regulation / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Immunoprecipitation
  • Luminescent Proteins / genetics
  • Mass Spectrometry
  • Mechanoreceptors / cytology*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Matrix-Associated Proteins / deficiency
  • Nuclear Matrix-Associated Proteins / genetics
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Nucleocytoplasmic Transport Proteins / deficiency
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Protein Binding / genetics
  • Signal Transduction / genetics
  • Synapses / genetics
  • Synapses / physiology*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • F-Box Proteins
  • FSN-1 protein, C elegans
  • Guanine Nucleotide Exchange Factors
  • Luminescent Proteins
  • Nuclear Matrix-Associated Proteins
  • Nucleocytoplasmic Transport Proteins
  • RAE1 protein, human
  • RPM-1 protein, C elegans
  • MYCBP2 protein, human
  • Ubiquitin-Protein Ligases
  • Glo-1 protein, C elegans
  • rab GTP-Binding Proteins