Truncated TrkB: beyond a dominant negative receptor

Cytokine Growth Factor Rev. Feb-Apr 2012;23(1-2):15-24. doi: 10.1016/j.cytogfr.2012.01.002. Epub 2012 Feb 15.

Abstract

BDNF activates trkB receptors to regulate neuronal survival, differentiation, and proliferation. Mutations in the BDNF gene, altered BDNF expression, and altered trkB expression are associated with degenerative and psychiatric disorders. The full-length trkB receptor (trkB.tk(+)) undergoes autophosphorylation to activate intracellular signaling pathways. The truncated trkB receptor (trkB.t1) is abundantly expressed in the brain but lacks the catalytic tyrosine kinase domain. TrkB.t1 is a dominant-negative receptor that inhibits trkB.tk(+) signaling. While this is an important function of trkB.t1, it is only one of its many functions. TrkB.t1 sequesters and translocate BDNF, induces filopodia and neurite outgrowth, stimulates intracellular signaling cascades, regulates Rho GTPase signaling, and modifies cytoskeletal structures. TrkB.t1 is an active signaling molecule with regulatory effects on neurons and astrocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / physiology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Brain-Derived Neurotrophic Factor / physiology
  • Central Nervous System / metabolism
  • Codon, Nonsense
  • Genes, Dominant / physiology*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / physiology
  • Models, Biological
  • Neurons / metabolism
  • Neurons / physiology
  • Receptor, trkB / chemistry
  • Receptor, trkB / genetics*
  • Receptor, trkB / metabolism
  • Receptor, trkB / physiology*
  • Tissue Distribution

Substances

  • Brain-Derived Neurotrophic Factor
  • Codon, Nonsense
  • Isoenzymes
  • Receptor, trkB