Biochemistry and physiological role of otoferlin

Kirsten, R

doi:10.53846/goediss-516

Cited by 1 publication

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References 100 publications

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“…As mentioned earlier (Introduction 1.5), in these experiments, hearing was restored in Vglut3 knock-out mice two weeks after AAV1-mediated replacement of Vglut3 via postnatal injection (Akil et al, 2012). Dr. Kirsten Reuter identified AAV2/1 with the gene of interest following a human β -actin promoter as suitable for protein expression in IHCs Reuter, 2012). Therefore I subcloned mouse Cabp2 transcription variant 1 (GeneBank:NM_013878; long Cabp2 isoform) into an AAV2/1 backbone (AAV-HBA-EWB) for the expression of C-terminally EGFP-tagged Cabp2.…”

Section: 14d)mentioning

confidence: 67%

The role of Calcium Binding Protein 2 in synaptic sound encoding and hearing

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Cochlear amplification is a process most pronounced in the mid-frequency region of the organ of Corti and is mainly governed by OHC function but also tectorial membrane flexibility (Legan et al., 2000).As mentioned above, OHC translate depolarization due to cation influx (primarily K + ) into terized by six C2-domains, most of which are able to bind Ca 2+ (except C2A domain;(Helfmann et al., 2011;Johnson and Chapman, 2010;Ramakrishnan et al., 2009)). Therefore, otoferlin is suggested to act as the Ca 2+ sensor, required for exocytosis at IHC ribbon synapses (Roux et al., 2006). In addition, otoferlin is required for vesicle replenishment possibly through promoting 1.3 Voltage-gated Ca 2+ channels VGCC possess the ability to convey changes in membrane potential into Ca 2+ influx in various cell types, i.e. nerve, muscle, some endocrine and sensory cells. Elevations in intracellular Ca 2+ levels trigger Ca 2+ -dependent signaling cascades and are crucial for excitation-secretion coupling , muscle excitation-contraction coupling, cell division, migration and differentiation. Moreover, loose regulation of VGCC gating can induce apoptosis due to Ca 2+ toxicity. Therefore, VGCC are regulated by sophisticated feedback mechanisms to control intracellular Ca 2+ levels. VGCC are classified into L-, N-, P/Q-, R-and T-types dependent on their subunit composition, electrophysiological and pharmacological properties and are comprised of a principal Ca V α1 subunit and 2-3 auxiliary subunits Ca V β , Ca V α 2 δ and Ca V γ (Figure 1.5A; reviewed in (Catterall, 2011;Neely and Hidalgo, 2014)). The Ca V α1 subunitThe Ca V α1 subunit is the pore forming subunit of VGCC is a polypeptide chain and comprised of four homologous repeats (I-IV) bridged by cytoplasmic loops. Every repeat has six transmembrane segments (S1-S6) of separate functions. To be able to respond to changes in membrane potential, VGCC are provided with a voltage sensor located in segment S4, which is comprised of four positively charged amino acids. Ca 2+ ions are able to enter the cell through the channel

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Section: 14d)mentioning

confidence: 67%

The role of Calcium Binding Protein 2 in synaptic sound encoding and hearing

Picher¹

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Biochemistry and physiological role of otoferlin

Cited by 1 publication

References 100 publications

The role of Calcium Binding Protein 2 in synaptic sound encoding and hearing

The role of Calcium Binding Protein 2 in synaptic sound encoding and hearing

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