title: Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.
abstract: In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near-complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane.
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shan Shan H
authors.initials: SSH
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Held
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Man Yan
authors.initials: MY
authors.lastname: Wong
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Changliang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Aziz
authors.initials: A
authors.lastname: Karakhanyan
authors.affiliation: Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kaeser@hms.harvard.edu.
authors.forename: Pascal S
authors.initials: PS
authors.lastname: Kaeser
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005089:Exocytosis; D008561:Membrane Fusion; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D057907:Post-Synaptic Density / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*; D020691:rab GTP-Binding Proteins
chemical_list: D018528:ATP-Binding Cassette Transporters; C512841:Abca4 protein, mouse; C498441:Bsn protein, mouse; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C486769:Erc1 protein, mouse; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C498631:Pclo protein, mouse; C540452:RIM-BP3 protein, mouse; D050600:SNARE Proteins; C503321:Unc13a protein, mouse; D020691:rab GTP-Binding Proteins