Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses.
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.
Johnson
Stuart L
SL
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Franz
Christoph
C
Kuhn
Stephanie
S
Furness
David N
DN
Rüttiger
Lukas
L
Münkner
Stefan
S
Rivolta
Marcelo N
MN
Seward
Elizabeth P
EP
Herschman
Harvey R
HR
Engel
Jutta
J
Knipper
Marlies
M
Marcotti
Walter
W
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
D050863:Synaptotagmin I; D050861:Synaptotagmin II; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins; D002118:Calcium