title: Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses.
abstract: Mammalian cochlear inner hair cells (IHCs) are specialized for the dynamic coding of continuous and finely graded sound signals. This ability is largely conferred by the linear Ca(2+) dependence of neurotransmitter release at their synapses, which is also a feature of visual and olfactory systems. The prevailing hypothesis is that linearity in IHCs occurs through a developmental change in the Ca(2+) sensitivity of synaptic vesicle fusion from the nonlinear (high order) Ca(2+) dependence of immature spiking cells. However, the nature of the Ca(2+) sensor(s) of vesicle fusion at hair cell synapses is unknown. We found that synaptotagmin IV was essential for establishing the linear exocytotic Ca(2+) dependence in adult rodent IHCs and immature outer hair cells. Moreover, the expression of the hitherto undetected synaptotagmins I and II correlated with a high-order Ca(2+) dependence in IHCs. We propose that the differential expression of synaptotagmins determines the characteristic Ca(2+) sensitivity of vesicle fusion at hair cell synapses.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Christoph
authors.initials: C
authors.lastname: Franz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kuhn
authors.forename: David N
authors.initials: DN
authors.lastname: Furness
authors.forename: Lukas
authors.initials: L
authors.lastname: Rüttiger
authors.forename: Stefan
authors.initials: S
authors.lastname: Münkner
authors.forename: Marcelo N
authors.initials: MN
authors.lastname: Rivolta
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Seward
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Herschman
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells; D003051:Cochlea / Q000166:cytology / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005089:Exocytosis / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005849:Gerbillinae; D049452:Green Fluorescent Proteins / Q000235:genetics; D006198:Hair Cells, Auditory / Q000166:cytology*; D016014:Linear Models; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000502:physiology* / Q000648:ultrastructure; D050863:Synaptotagmin I / Q000235:genetics / Q000378:metabolism; D050861:Synaptotagmin II / Q000235:genetics / Q000378:metabolism; D050857:Synaptotagmins / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods
chemical_list: D050863:Synaptotagmin I; D050861:Synaptotagmin II; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins; D002118:Calcium