Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling

Frank, Thomas; Rutherford, Mark A.; Strenzke, Nicola; Neef, Andreas; Pangršič, Tina; Khimich, Darina; Fejtová, Anna; Gundelfinger, Eckart D.; Liberman, M. Charles; Harke, Benjamin; Bryan, Keith E.; Lee, Amy; Egner, Alexander; Riedel, Dietmar; Moser, Tobias

doi:10.1016/j.neuron.2010.12.020

Cited by 62 publications

(178 citation statements)

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“…Consequently, normally transient SV stages, such as docking, might become more frequent in the course of prolonged stimulation, which entails a slowdown of exocytosis. Compatible with this, docked SVs in the mutant were mainly found within 60 nm laterally to the presynaptic density, close to Ca 2+ channel clusters in mature IHC ribbon synapses [21,25,50]. Moreover, tethers appeared on average shorter at inhibited and stimulated Otof Pga/Pga AZs compared to rest, which might have a different underlying mechanism.…”

Section: Filaments Association Defines Sv Sub-pools At Ihc Az-membranmentioning

confidence: 62%

“…Beside the filaments connecting SVs at and to the synaptic ribbon, earlier studies have highlighted the presence of tethers in association with SVs at the AZ-membrane of IHC ribbon synapses [21,[23][24][25]. To our knowledge, changes in SV tethering at IHC ribbon synapses have not yet been targeted under different activity states.…”

Section: Classification Of Mp-svs Based On Their Association With Tetmentioning

confidence: 99%

“…The presynaptic density at IHC ribbon synapses contains the large scaffold protein bassoon [21,27,50] to organize Ca 2+ channels and promote vesicle refilling [21]. It was found previously by using electron tomography on conventionally fixed wild-type and bassoon-deficient IHC ribbon synapses that the presence of a synaptic ribbon seems to increase the number of membrane-attached tethers [21]. In RIBEYE KO mice, ribbons are absent in IHCs [25,55].…”

Section: Filaments Association Defines Sv Sub-pools At Ihc Az-membranmentioning

confidence: 99%

“…The phenomenon of SVs within synaptic terminals having interconnections among each other has been described using different electron microscopic techniques [13,[15][16][17][18]. Moreover, filaments broadly termed as tethers, linking SVs to the AZ-membrane were observed in synapses of various organisms, across several types of synaptic preparations, such as conventional synapses or cochlear inner hair cells (IHCs) [9,13,[19][20][21][22][23][24][25]. These tethers differ strikingly in length [13,15,20,23,26] and morphology [9,15,25], whereby a connection via several short tethers seems to appear shortly before SV fusion at conventional AZ-membranes [20].…”

Section: Introductionmentioning

confidence: 99%

“…In otoferlin KOs, IHC exocytosis is almost completely abolished [39], but ribbon synapse morphology appeared unchanged, and ribbons were normally attached to the AZ via the presynaptic density [23]. The presynaptic density is an electron-dense structure mediating ribbon anchorage involving the scaffold protein bassoon [21]. In stark contrast to the KO, in the otoferlin pachanga (Otof Pga/Pga ) mutant, which carries a missense mutation in the C 2 F domain [40], IHC exocytosis in response to 10 ms depolarization remained normal.…”

Section: Introductionmentioning

confidence: 99%

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Vesicle sub‐pool organization at inner hair cell ribbon synapses

2018

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The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically discernable pools, linked via filaments to the ribbon or the presynaptic membrane. We propose that filaments play a major role in SV resupply and exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that SVs are organized in sub-pools defined by the filament number per vesicle and its connections. Upon stimulation, SVs increasingly linked to other vesicles and to the ribbon, whereas single-tethered SVs dominated at the membrane. Mutant mice for the hair cell protein otoferlin (, ) are profoundly deaf with reduced sustained release, serving as a model to investigate the SV replenishment at IHCs. Upon stimulation, multiple-tethered and docked vesicles (rarely observed in wild-type) accumulated at active zones due to an impairment downstream of docking. Conclusively, vesicles are organized in sub-pools at ribbon-type active zones by filaments to support vesicle supply, transport, and finally release.

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Section: Filaments Association Defines Sv Sub-pools At Ihc Az-membranmentioning

confidence: 62%

Section: Classification Of Mp-svs Based On Their Association With Tetmentioning

confidence: 99%

Section: Filaments Association Defines Sv Sub-pools At Ihc Az-membranmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Vesicle sub‐pool organization at inner hair cell ribbon synapses

2018

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Balancing presynaptic release and endocytic membrane retrieval at hair cell ribbon synapses

Pangršič

Vogl

2018

FEBS Letters

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The timely and reliable processing of auditory and vestibular information within the inner ear requires highly sophisticated sensory transduction pathways. On a cellular level, these demands are met by hair cells, which respond to sound waves – or alterations in body positioning – by releasing glutamate‐filled synaptic vesicles (SVs) from their presynaptic active zones with unprecedented speed and exquisite temporal fidelity, thereby initiating the auditory and vestibular pathways. In order to achieve this, hair cells have developed anatomical and molecular specializations, such as the characteristic and name‐giving ‘synaptic ribbons’ – presynaptically anchored dense bodies that tether SVs prior to release – as well as other unique or unconventional synaptic proteins. The tightly orchestrated interplay between these molecular components enables not only ultrafast exocytosis, but similarly rapid and efficient compensatory endocytosis. So far, the knowledge of how endocytosis operates at hair cell ribbon synapses is limited. In this Review, we summarize recent advances in our understanding of the SV cycle and molecular anatomy of hair cell ribbon synapses, with a focus on cochlear inner hair cells.

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Quantitative analysis of ribbons, vesicles, and cisterns at the cat inner hair cell synapse: Correlations with spontaneous rate

Kantardzhieva

Liberman

Sewell

2013

J of Comparative Neurology

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Cochlear hair cells form ribbon synapses with terminals of the cochlear nerve. To test the hypothesis that one function of the ribbon is to create synaptic vesicles from the cisternal structures that are abundant at the base of hair cells, we analyzed the distribution of vesicles and cisterns around ribbons from serial sections of inner hair cells in the cat, and compared data from low and high spontaneous rate (SR) synapses. Consistent with the hypothesis, we identified a “sphere of influence” of 350 nm around the ribbon, with fewer cisterns and many more synaptic vesicles. Although high- and low-SR ribbons tended to be longer and thinner than high-SR ribbons, the total volume of the two ribbon types was similar. There were almost as many vesicles docked at the active zone as attached to the ribbon. The major SR-related difference was that low-SR ribbons had more synaptic vesicles intimately associated with them. Our data suggest a trend in which low-SR synapses had more vesicles attached to the ribbon (51.3 vs. 42.8), more docked between the ribbon and the membrane (12 vs. 8.2), more docked at the active zone (56.9 vs. 44.2), and more vesicles within the “sphere of influence” (218 vs. 166). These data suggest that the structural differences between high-and low-SR synapses may be more a consequence, than a determinant, of the physiological differences.

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Bassoon and the Synaptic Ribbon Organize Ca2+ Channels and Vesicles to Add Release Sites and Promote Refilling

Cited by 62 publications

References 0 publications

Vesicle sub‐pool organization at inner hair cell ribbon synapses

Vesicle sub‐pool organization at inner hair cell ribbon synapses

Balancing presynaptic release and endocytic membrane retrieval at hair cell ribbon synapses

Quantitative analysis of ribbons, vesicles, and cisterns at the cat inner hair cell synapse: Correlations with spontaneous rate

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