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

Eiko K. de Jong, Jonathan Vinet, Vesna S. Stanulovic, Michel Meijer, Evelyn Wesseling, Klaas Sjollema, Hendrikus W. G. M. Boddeke, Knut Biber*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4136-4145
Number of pages10
JournalThe FASEB Journal
Volume22
Issue number12
DOIs
Publication statusPublished - Dec-2008

Keywords

  • chemokines
  • neuroimmunology
  • vesicles
  • microglia
  • neuronal injury
  • neuron-glia communication
  • REGULATED SECRETORY PATHWAY
  • NERVOUS-SYSTEM
  • GROWTH-FACTOR
  • PC12 CELLS
  • RAT-BRAIN
  • MICROGLIA
  • CHEMOKINES
  • GRANULES
  • NEUROPEPTIDES
  • MOTOR

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