title: Release mode of large and small dense-core vesicles specified by different synaptotagmin isoforms in PC12 cells.
abstract: Many cells release multiple substances in different proportions according to the specific character of a stimulus. PC12 cells, a model neuroendocrine cell line, express multiple isoforms of the exocytotic Ca(2+) sensor synaptotagmin. We show that these isoforms sort to populations of dense-core vesicles that differ in size. These synaptotagmins differ in their Ca(2+) sensitivities, their preference for full fusion or kiss-and-run, and their sensitivity to inhibition by synaptotagmin IV. In PC12 cells, vesicles that harbor these different synaptotagmin isoforms can be preferentially triggered to fuse by different forms of stimulation. The mode of fusion is specified by the synaptotagmin isoform activated, and because kiss-and-run exocytosis can filter small molecules through a size-limiting fusion pore, the activation of isoforms that favor kiss-and-run will select smaller molecules over larger molecules packaged in the same vesicle. Thus synaptotagmin isoforms can provide multiple levels of control in the release of different molecules from the same cell.
authors.affiliation: Department of Physiology, University of Wisconsin School of Medical and Public Health, Madison, WI 53706, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: F Mark
authors.initials: FM
authors.lastname: Dunning
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rehfuss
authors.forename: Deepshika
authors.initials: D
authors.lastname: Ramanan
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Chapman
authors.forename: Meyer B
authors.initials: MB
authors.lastname: Jackson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D008561:Membrane Fusion / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016716:PC12 Cells; D020033:Protein Isoforms / Q000378:metabolism*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D012680:Sensitivity and Specificity; D050863:Synaptotagmin I / Q000378:metabolism*; D050857:Synaptotagmins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D050863:Synaptotagmin I; D050857:Synaptotagmins; D002118:Calcium