Synaptotagmin IV determines the linear [Ca.sup.2+] dependence of vesicle fusion at auditory ribbon synapses

• Published in: Nature neuroscience Vol. 13; no. 1; pp. 45 - 54
• Main Authors: Johnson, Stuart L, Franz, Christoph, Kuhn, Stephanie, Furness, David N, Ruttiger, Lukas, Munkner, Stefan, Rivolta, Marcelo N, Seward, Elizabeth P, Herschman, Harvey R, Engel, Jutta, Knipper, Marlies, Marcotti, Walter
• Format: Journal Article
• Language: English
• Published: Nature Publishing Group 01.01.2010
• Subjects: Genetic aspects; Hair; Hair cells (Mechanoreceptors); Neurotransmitters; Physiological aspects; Synapses; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2456

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.sup.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.sup.2+] sensitivity of synaptic vesicle fusion from the nonlinear (high order) [Ca.sup.2+] dependence of immature spiking cells. However, the nature of the [Ca.sup.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.sup.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.sup.2+] dependence in IHCs. We propose that the differential expression of synaptotagmins determines the characteristic [Ca.sup.2+] sensitivity of vesicle fusion at hair cell synapses.