Arginine Methylation by PRMT2 Controls the Functions of the Actin Nucleator Cobl

Dev Cell. 2018 Apr 23;45(2):262-275.e8. doi: 10.1016/j.devcel.2018.03.007.


The complex architecture of neuronal networks in the brain requires tight control of the actin cytoskeleton. The actin nucleator Cobl is critical for neuronal morphogenesis. Here we reveal that Cobl is controlled by arginine methylation. Coprecipitations, coimmunoprecipitations, cellular reconstitutions, and in vitro reconstitutions demonstrated that Cobl associates with the protein arginine methyltransferase PRMT2 in a Src Homology 3 (SH3) domain-dependent manner and that this promotes methylation of Cobl's actin nucleating C-terminal domain. Consistently, PRMT2 phenocopied Cobl functions in both gain- and loss-of-function studies. Both PRMT2- and Cobl-promoted dendritogenesis relied on methylation. PRMT2 effects require both its catalytic domain and SH3 domain. Cobl-mediated dendritic arborization required PRMT2, complex formation with PRMT2, and PRMT2's catalytic activity. Mechanistic studies reveal that Cobl methylation is key for Cobl actin binding. Therefore, arginine methylation is a regulatory mechanism reaching beyond controlling nuclear processes. It also controls a major, cytosolic, cytoskeletal component shaping neuronal cells.

Keywords: Cordon bleu; PRMT2 interaction partner and substrate; WH2 domain; actin nucleation; arginine methylation; arginine methyltransferase; dendritogenesis; neuronal network formation; posttranslational modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Animals
  • Arginine / metabolism*
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Female
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins
  • Neurons / cytology
  • Neurons / metabolism*
  • Protein Processing, Post-Translational
  • Protein-Arginine N-Methyltransferases / genetics
  • Protein-Arginine N-Methyltransferases / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Two-Hybrid System Techniques


  • Cobl protein, mouse
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Microfilament Proteins
  • Proteins
  • Arginine
  • PRMT2 protein, human
  • PRMT2 protein, mouse
  • Protein-Arginine N-Methyltransferases