title: Prodynorphin storage and processing in axon terminals and dendrites.
abstract: The classical view postulates that neuropeptide precursors in neurons are processed into mature neuropeptides in the somatic trans-Golgi network (TGN) and in secretory vesicles during axonal transport. Here we show that prodynorphin (PDYN), precursor to dynorphin opioid peptides, is predominantly located in axon terminals and dendrites in hippocampal and striatal neurons. The molar content of unprocessed PDYN was much greater than that of dynorphin peptides in axon terminals of PDYN-containing neurons projecting to the CA3 region of the hippocampus and in the striatal projections to the ventral tegmental area. Electron microscopy showed coexistence of PDYN and dynorphins in the same axon terminals with occasional codistribution in individual dense core vesicles. Thus, the precursor protein is apparently stored at presynaptic sites. In comparison with the hippocampus and striatum, PDYN and dynorphins were more equally distributed between neuronal somata and processes in the amygdala and cerebral cortex, suggesting regional differences in the regulation of trafficking and processing of the precursor protein. Potassium-induced depolarization activated PDYN processing and secretion of opioid peptides in neuronal cultures and in a model cell line. Regulation of PDYN storage and processing at synapses by neuronal activity or extracellular stimuli may provide a local mechanism for regulation of synaptic transmission.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Yakovleva
authors.forename: Igor
authors.initials: I
authors.lastname: Bazov
authors.forename: Gvido
authors.initials: G
authors.lastname: Cebers
authors.forename: Zoya
authors.initials: Z
authors.lastname: Marinova
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hara
authors.forename: Aisha
authors.initials: A
authors.lastname: Ahmed
authors.forename: Mila
authors.initials: M
authors.lastname: Vlaskovska
authors.forename: Björn
authors.initials: B
authors.lastname: Johansson
authors.forename: Ute
authors.initials: U
authors.lastname: Hochgeschwender
authors.forename: Indrapal N
authors.initials: IN
authors.lastname: Singh
authors.forename: Annadora J
authors.initials: AJ
authors.lastname: Bruce-Keller
authors.forename: Yasmin L
authors.initials: YL
authors.lastname: Hurd
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.forename: Lars
authors.initials: L
authors.lastname: Terenius
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Ekström
authors.forename: Kurt F
authors.initials: KF
authors.lastname: Hauser
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Pickel
authors.forename: Georgy
authors.initials: G
authors.lastname: Bakalkin
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000166:cytology; D001921:Brain / Q000166:cytology; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D004745:Enkephalins / Q000032:analysis / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008854:Microscopy, Electron; D009474:Neurons / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism*; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin