Interaction proteomics identify NEURL4 and the HECT E3 ligase HERC2 as novel modulators of centrosome architecture

Mol Cell Proteomics. 2012 Jun;11(6):M111.014233. doi: 10.1074/mcp.M111.014233. Epub 2012 Jan 19.


Centrosomes are composed of a centriole pair surrounded by an intricate proteinaceous matrix referred to as pericentriolar material. Although the mechanisms underpinning the control of centriole duplication are now well understood, we know relatively little about the control of centrosome size and shape. Here we used interaction proteomics to identify the E3 ligase HERC2 and the neuralized homologue NEURL4 as novel interaction partners of the centrosomal protein CP110. Using high resolution imaging, we find that HERC2 and NEURL4 localize to the centrosome and that interfering with their function alters centrosome morphology through the appearance of aberrant filamentous structures that stain for a subset of pericentriolar material proteins including pericentrin and CEP135. Using an RNA interference-resistant transgene approach in combination with structure-function analyses, we show that the association between CP110 and HERC2 depends on nonoverlapping regions of NEURL4. Whereas CP110 binding to NEURL4 is dispensable for the regulation of pericentriolar material architecture, its association with HERC2 is required to maintain normal centrosome integrity. NEURL4 is a substrate of HERC2, and together these results indicate that the NEURL4-HERC2 complex participates in the ubiquitin-dependent regulation of centrosome architecture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / isolation & purification
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism
  • Centrosome / metabolism*
  • Chromatography, Affinity
  • Gene Knockdown Techniques
  • Guanine Nucleotide Exchange Factors / isolation & purification
  • Guanine Nucleotide Exchange Factors / metabolism*
  • HEK293 Cells
  • Humans
  • Microtubule-Associated Proteins / isolation & purification
  • Microtubule-Associated Proteins / metabolism
  • Phosphoproteins / metabolism
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Protein Transport
  • Proteomics
  • RNA Interference
  • Ubiquitin-Protein Ligases
  • Ubiquitination


  • CCP110 protein, human
  • CEP97 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • HERC2 protein, human
  • Neurl4 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex