Exocytosis of glutamate from cochlear inner hair cell

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R-MMU-9664156
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Reaction [omitted]
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Mus musculus
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5/5
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SVG |   | PPTX  | SBGN
Exocytosis of glutamate from cochlear inner hair cell
An influx of calcium ions into the inner hair cell activates exocytosis of glutamate from vesicles docked near ribbon structures on the inner face of the plasma membrane (Roux et al. 2006, Ramakrishnan et al. 2014). Glutamate vesicles of inner hair cells have Otoferlin (OTOF) rather than a synaptotagmin on their surfaces as a calcium sensitive trigger for fusion with the plasma membrane (Roux et al. 2006, Ramakrishnan et al. 2009, Johnson and Chapman 2010, Ramakrishnan et al. 2014, Vincent et al. 2014, Hams et al. 2017, Michalski et al. 2017). Otoferlin interacts with the SNARE proteins Stx1a and Snap25 on the plasma membrane (Ramakrishnan et al. 2009, Johnson and Chapman 2010, Ramakrishnan et al. 2014). The ribbon structure contains Ribeye (a splice variant of Ctbp2, Maxeiner et al. 2016), Piccolino (a short variant of Piccolo, Regus-Leidig et al. 2013), and Bassoon (Khimich et al. 2005), which links the structure to the plasma membrane (tom Dieck et al. 2005), colocalizes calcium channels and vesicles, and promotes replenishment of vesicles (Frank et al. 2010).
Literature References
PubMed ID Title Journal Year
26929012 How to make a synaptic ribbon: RIBEYE deletion abolishes ribbons in retinal synapses and disrupts neurotransmitter release

Südhof, TC, Maxeiner, S, Luo, F, Schmitz, F, Tan, A

EMBO J. 2016
15728193 Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex

Bracko, O, Gundelfinger, ED, Brandstätter, JH, Tom Dieck, S, Brauner, D, Regus, H, Kessels, MM, Altrock, WD, Qualmann, B, Fejtová, A

J. Cell Biol. 2005
21092861 Bassoon and the synaptic ribbon organize Ca²+ channels and vesicles to add release sites and promote refilling

Neef, A, Strenzke, N, Liberman, MC, Gundelfinger, ED, Harke, B, Rutherford, MA, Lee, A, Fetjova, A, Bryan, KE, Riedel, D, Frank, T, Fejtová, A, Moser, T, Khimich, D, Egner, A, Pangršič, T

Neuron 2010
24478316 Calcium regulates molecular interactions of otoferlin with soluble NSF attachment protein receptor (SNARE) proteins required for hair cell exocytosis

Drescher, DG, Drescher, MJ, Morley, BJ, Kelley, PM, Ramakrishnan, NA

J. Biol. Chem. 2014
20921140 Otoferlin is a calcium sensor that directly regulates SNARE-mediated membrane fusion

Chapman, ER, Johnson, CP

J. Cell Biol. 2010
15829963 Hair cell synaptic ribbons are essential for synchronous auditory signalling

Gundelfinger, ED, Tom Dieck, S, Pujol, R, Nouvian, R, Moser, T, Khimich, D, Egner, A

Nature 2005
17055430 Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse

Petit, C, Bahloul, A, Nouvian, R, Grati, M, Triller, A, Rostaing, P, Hamard, G, Simmler, MC, Safieddine, S, Moser, T, Avan, P, Le Gall, M, Roux, I, Perfettini, I

Cell 2006
25122888 Exocytotic machineries of vestibular type I and cochlear ribbon synapses display similar intrinsic otoferlin-dependent Ca2+ sensitivity but a different coupling to Ca2+ channels

Petit, C, Dulon, D, Safieddine, S, Vincent, PF, Bouleau, Y

J. Neurosci. 2014
23936420 Identification and immunocytochemical characterization of Piccolino, a novel Piccolo splice variant selectively expressed at sensory ribbon synapses of the eye and ear

Gundelfinger, ED, Sedmak, T, Brandstätter, JH, Kremers, J, Ott, C, Regus-Leidig, H, Atorf, J, Fuchs, M, Fejtová, A, Löhner, M

PLoS ONE 2013
19004828 Direct interaction of otoferlin with syntaxin 1A, SNAP-25, and the L-type voltage-gated calcium channel Cav1.3

Drescher, DG, Drescher, MJ, Ramakrishnan, NA

J. Biol. Chem. 2009
28696301 Otoferlin is a multivalent calcium-sensitive scaffold linking SNAREs and calcium channels

Hams, N, Qiu, W, Padmanarayana, M, Johnson, CP

Proc. Natl. Acad. Sci. U.S.A. 2017
29111973 Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses

Petit, C, Ciric, D, Hardelin, JP, Guillon, M, Bahloul, A, Goutman, JD, Tertrais, M, Boutet de Monvel, J, Sachse, M, Parrin, A, Rothman, JE, Nouaille, S, Michalski, N, Safieddine, S, Dulon, D, Krishnakumar, SS, Sutton, RB, Avan, P, Emptoz, A, Auclair, SM

Elife 2017
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