title: Expression, transport, and axonal sorting of neuronal CCL21 in large dense-core vesicles.
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.
authors.affiliation: Department of Medical Physiology, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, 9713AV Groningen, The Netherlands.
authors.forename: Eiko K
authors.initials: EK
authors.lastname: de Jong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vinet
authors.forename: Vesna S
authors.initials: VS
authors.lastname: Stanulovic
authors.forename: Michel
authors.initials: M
authors.lastname: Meijer
authors.forename: Evelyn
authors.initials: E
authors.lastname: Wesseling
authors.forename: Klaas
authors.initials: K
authors.lastname: Sjollema
authors.forename: Hendrikus W G M
authors.initials: HW
authors.lastname: Boddeke
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D022142:Secretory Vesicles / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D054421:Chemokine CCL21; D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins