Skip to Main content Skip to Navigation
Theses

L’organisation spatiale des canaux calciques cav1.3 détermine l’efficacité de l’exocytose des synapses à ruban dans les cellules ciliées de l’oreille interne

Philippe Vincent 1
1 Neurophysiologie de la Synapse Auditive
UB - Université de Bordeaux, INSERM - Institut National de la Santé et de la Recherche Médicale : U1120, CHU de Bordeaux Pellegrin [Bordeaux], Neuroscience Institute
Abstract : Cochlear inner hair cells (IHCs) encode acoustic signals into nerve impulses at their ribbon synapses formed with the auditory afferent fibers. The exocytosis of glutamatergic vesicles is triggered by voltage activation of Cav1.3 channels and requires otoferlin, the putative intracellular Ca2+ sensor. The precise molecular mechanisms of exocytosis still remain elusive, notably the mechanisms allowing the temporal precision, the high rates of vesicular fusion (high frequency phase-locking with sound) and the indefatigability of the process. We show here that exocytosis in auditory and vestibular hair cells relies on a specific tight spatial organization of Cav1.3 channels at the active zones. Auditory IHCs use different Cav1.3isoforms, notably short C-terminal isoforms (Cav1.343S et Cav1.342A). These short Cav1.3isoforms essentially trigger the RRP exocytosis (Readily Releasable Pool of vesicles) and are at the origin of its fast adaptation. This fast exocytotic adaptation is based both on an intracellularCa2+ dependant inactivation of the Ca2+ current and on its extracellular block by exocytosed protons. Long Cav1.3 isoforms (Cav1.342L et Cav1.3∆44) regulate the vesicular recruitment at the active zones. Furthermore, our results show that a synaptic actin cytoskeleton is essential for the tight spatial organization of the Cav1.3 channels at the ribbons. Clarin 1 (Usher IIIA protein),through its interactions with the F-actin network, harmonin (PDZ protein, Usher IC) and the Ca2+channel β2 subunit, is required to maintain the tight organization of Cav1.3 channels at the ribbon synapses.
Document type :
Theses
Complete list of metadatas

Cited literature [473 references]  Display  Hide  Download

https://tel.archives-ouvertes.fr/tel-01969394
Contributor : Abes Star :  Contact
Submitted on : Friday, January 4, 2019 - 9:52:07 AM
Last modification on : Wednesday, May 1, 2019 - 1:31:20 AM
Long-term archiving on: : Friday, April 5, 2019 - 1:01:11 PM

File

VINCENT_PHILIPPE_2015.pdf
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01969394, version 1

Citation

Philippe Vincent. L’organisation spatiale des canaux calciques cav1.3 détermine l’efficacité de l’exocytose des synapses à ruban dans les cellules ciliées de l’oreille interne. Biologie cellulaire. Université de Bordeaux, 2015. Français. ⟨NNT : 2015BORD0238⟩. ⟨tel-01969394⟩

Share

Metrics

Record views

1515

Files downloads

698