The spliceosome-associated protein Mfap1 binds to VCP in Drosophila

PLoS One. 2017 Aug 24;12(8):e0183733. doi: 10.1371/journal.pone.0183733. eCollection 2017.

Abstract

Posttranscriptional regulation of gene expression contributes to many developmental transitions. Previously, we found that the AAA chaperone Valosin-Containing Protein (VCP) regulates ecdysone-dependent dendrite pruning of Drosophila class IV dendritic arborization (c4da) neurons via an effect on RNA metabolism. In a search for RNA binding proteins associated with VCP, we identified the spliceosome-associated protein Mfap1, a component of the tri-snRNP complex. Mfap1 is a nucleolar protein in neurons and its levels are regulated by VCP. Mfap1 binds to VCP and TDP-43, a disease-associated RNA-binding protein. via distinct regions in its N- and C-terminal halfs. Similar to vcp mutations, Mfap1 overexpression causes c4da neuron dendrite pruning defects and mislocalization of TDP-43 in these cells, but genetic analyses show that Mfap1 is not a crucial VCP target during dendrite pruning. Finally, rescue experiments with a lethal mfap1 mutant show that the VCP binding region is not essential for Mfap1 function, but may act to increase its stability or activity.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Contractile Proteins / metabolism*
  • Down-Regulation
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Mutation
  • Neurons / metabolism
  • Nucleotides / metabolism
  • Protein Binding
  • RNA Splicing Factors
  • Spliceosomes / metabolism*
  • Valosin Containing Protein

Substances

  • Contractile Proteins
  • Drosophila Proteins
  • Extracellular Matrix Proteins
  • Nucleotides
  • RNA Splicing Factors
  • microfibrillar protein
  • Adenosine Triphosphatases
  • Valosin Containing Protein
  • ter94 protein, Drosophila

Grants and funding

This study was supported by the DFG Cluster of Excellence „Cells in Motion“ (EXC1003).The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.