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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.07-101907v1 22/12/4136    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by de Jong, E. K. Articles by Biber, K. Search for Related Content PubMed PubMed Citation Articles by de Jong, E. K. Articles by Biber, K.

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

Eiko K. de Jong^*,1, Jonathan Vinet^*,1, Vesna S. Stanulovic^*,1, Michel Meijer^*, Evelyn Wesseling^*, Klaas Sjollema, Hendrikus W. G. M. Boddeke^* and Knut Biber^*,2

^* Department of Medical Physiology and

University Medical Imaging Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

²Correspondence: Department of Medical Physiology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713AV Groningen, The Netherlands. E-mail: k.p.h.biber{at}med.umcg.nl

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.—De Jong, E. K., Vinet, J., Stanulovic, V. S., Meijer, M., Wesseling, E., Sjollema, K., Boddeke, H. W. G. M., Biber, K. Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles.

Key Words: chemokines • neuroimmunology • vesicles • microglia • neuronal injury • neuron-glia communication