Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles

FASEB J. 2008 Dec;22(12):4136-45. doi: 10.1096/fj.07-101907. Epub 2008 Aug 12.


Neurons are highly polarized cells, and neuron-neuron communication is based on directed transport and release of neurotransmitters, neuropeptides, and neurotrophins. Directed communication may also be attributed to neuron-microglia signaling, since neuronal damage can induce a microglia reaction at specific sites only. However, the mechanism underlying this site-specific microglia reaction is not yet understood. Neuronal CCL21 is a microglia-activating chemokine, which in brain is solely found in endangered neurons and is therefore a candidate for neuron-microglia signaling. Here we present that neuronal CCL21 is sorted into large dense-core vesicles, the secretory granules of the regulated release pathway of neurons. Live-cell imaging studies show preferential sorting of CCL21-containing vesicles into axons, indicating its directed transport. Thus, mouse neurons express and transport a microglia activating factor very similar to signaling molecules used in neuron-neuron communication. These data show for the first time the directed transport of a microglia activating factor in neurons and corroborate the function of neuronal CCL21 in directed neuron-microglia communication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Line, Tumor
  • Chemokine CCL21 / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Neurons / metabolism
  • Protein Transport
  • Recombinant Fusion Proteins / biosynthesis
  • Secretory Vesicles / metabolism*
  • Signal Transduction
  • Transfection


  • Chemokine CCL21
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins