Disruption of Trim9 function abrogates macrophage motility in vivo

J Leukoc Biol. 2017 Dec;102(6):1371-1380. doi: 10.1189/jlb.1A0816-371R. Epub 2017 Oct 11.


The vertebrate immune response comprises multiple molecular and cellular components that interface to provide defense against pathogens. Because of the dynamic complexity of the immune system and its interdependent innate and adaptive functionality, an understanding of the whole-organism response to pathogen exposure remains unresolved. Zebrafish larvae provide a unique model for overcoming this obstacle, because larvae are protected against pathogens while lacking a functional adaptive immune system during the first few weeks of life. Zebrafish larvae were exposed to immune agonists for various lengths of time, and a microarray transcriptome analysis was executed. This strategy identified known immune response genes, as well as genes with unknown immune function, including the E3 ubiquitin ligase tripartite motif-9 (Trim9). Although trim9 expression was originally described as "brain specific," its expression has been reported in stimulated human Mϕs. In this study, we found elevated levels of trim9 transcripts in vivo in zebrafish Mϕs after immune stimulation. Trim9 has been implicated in axonal migration, and we therefore investigated the impact of Trim9 disruption on Mϕ motility and found that Mϕ chemotaxis and cellular architecture are subsequently impaired in vivo. These results demonstrate that Trim9 mediates cellular movement and migration in Mϕs as well as neurons.

Keywords: chemotaxis; leukocyte; ubiquitin; zebrafish.

Publication types

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

MeSH terms

  • Animals
  • Cell Movement* / genetics
  • Cell Shape
  • Chemotaxis
  • Humans
  • Macrophages / cytology*
  • Macrophages / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism*
  • U937 Cells
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Zebrafish / genetics
  • Zebrafish / immunology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Nerve Tissue Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • Zebrafish Proteins
  • Trim9 protein, zebrafish
  • Ubiquitin-Protein Ligases