Molecular dissection of the photoreceptor ribbon synapse

Dieck, Susanne tom; Altrock, Wilko D.; Kessels, Michael M.; Qualmann, Britta; Regus, Hanna; Brauner, Dana; Fejtová, Anna; Bracko, Oliver; Gundelfinger, Eckart D.; Brandstätter, Johann Helmut

doi:10.1083/jcb.200408157

Cited by 361 publications

(225 citation statements)

References 42 publications

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“…Our hypothesis is that adhesion molecules that keep hair cells and their post-synaptic partners together also localize ribbons at the active zone juxtaposed to afferent fibers. This is perhaps accomplished indirectly through binding the cytomatrix protein Bassoon, because ribbons in bassoon mutants are found to be floating (Khimich et al, 2005;tom Dieck et al, 2005). As hair cells mature and synapses are formed, any ribbons that do not get localized at the membrane are likely degraded; therefore, we see a decrease in total ribbon number in mature hair cells during regeneration.…”

Section: Discussionmentioning

confidence: 86%

“…Failure to properly form and localize ribbons at the synapse leads to impaired synaptic transmission and sensory input propagation. Mice defective for bassoon, a cytomatrix protein thought to anchor ribbons at the synapse, show reduced exocytosis in auditory mechanosensory hair cells, reduced reliability of spiking at the auditory stimulus onset, abnormal auditory brain responses and lower amplitudes of b-wave responses during electroretinographic recordings in the eye (Brandstatter et al, 1999;Dick et al, 2003;Khimich et al, 2005;tom Dieck et al, 2005;Buran et al, 2010). Zebrafish larvae in which ribeye b, a gene coding for a major scaffolding protein in synaptic ribbons (Schmitz et al, 2000;Zenisek et al, 2004;Wan et al, 2005;Magupalli et al, 2008), is knocked down show reduction in the number of spikes of afferent neurons of the lateral line mechanosensory hair cells when the hair cells are stimulated (Sheets et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

Suli

Pujol

Cunningham

et al. 2016

Journal of Cell Science

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Failure to form proper synapses in mechanosensory hair cells, the sensory cells responsible for hearing and balance, leads to deafness and balance disorders. Ribbons are electron-dense structures that tether synaptic vesicles to the presynaptic zone of mechanosensory hair cells where they are juxtaposed with the post-synaptic endings of afferent fibers. They are initially formed throughout the cytoplasm, and, as cells mature, ribbons translocate to the basolateral membrane of hair cells to form functional synapses. We have examined the effect of post-synaptic elements on ribbon formation and maintenance in the zebrafish lateral line system by observing mutants that lack hair cell innervation, wild-type larvae whose nerves have been transected and ribbons in regenerating hair cells. Our results demonstrate that innervation is not required for initial ribbon formation but suggest that it is crucial for regulating the number, size and localization of ribbons in maturing hair cells, and for ribbon maintenance at the mature synapse.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

Suli

Pujol

Cunningham

et al. 2016

Journal of Cell Science

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“…In contrast to CtBP1, the N-terminal sequences of the CtBP2 isoforms might be critically important for their differential localization. The CtBP2 isoform RIBEYE is a large (985 amino acids) cytoplasmic protein that is exclusively expressed at synaptic ribbons of the central nervous system (9,31,44). RIBEYE contains a large N-terminal domain (560 amino acids) fused to a C-terminal (425 amino acid) region of CtBP2, resulting in a precise deletion of the N-terminal 20 amino acids of CtBP2 (see Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, the existence of an intrinsic acyltransferase activity of CtBP1-S remains controversial (30). In the retina, the photoreceptor ribbon synaptic complex contains RIBEYE (9) and CtBP1 (31). RIBEYE and CtBP1 are important for the assembly and function of central nervous system synapses.…”

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confidence: 99%

Acetylation by p300 Regulates Nuclear Localization and Function of the Transcriptional Corepressor CtBP2

Zhao

Subramanian

Zhou

et al. 2006

Journal of Biological Chemistry

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CtBP family members, CtBP1 and CtBP2, are unique transcriptional regulators that adapt a metabolic enzyme fold, and their activities are regulated by NAD(H)-binding. CtBP1 is both cytoplasmic and nuclear, and its subcellular localization is regulated by sumoylation, phosphorylation, and binding to a PDZ protein. In contrast, we showed that CtBP2 is exclusively nuclear. CtBP1 and CtBP2 are highly similar, but differ at the N-terminal 20 amino acid region. Substitution of the N-terminal domain of CtBP1 with the corresponding CtBP2 domain confers a dominant nuclear localization pattern to CtBP1. The N-terminal domain of CtBP2 contains three Lys residues. Our results show that these Lys residues are acetylated by the nuclear acetylase p300. Although all three Lys residues of CtBP2 (Lys-6, Lys-8, and Lys-10) appear to be acetylated, acetylation of Lys-10 is critical for nuclear localization. CtBP2 with a single amino acid substitution at Lys-10 (K10R) is predominantly localized in the cytoplasm. The cytoplasmic localization of the K10R mutant is correlated with enhanced nuclear export that is inhibited by leptomycin B. Furthermore, lack of acetylation at Lys-10 renders CtBP2 to be more efficient in repression of the E-cadherin promoter. Our studies have revealed the important roles of acetylation in regulating subcellular localization and transcriptional activity of CtBP2.

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“…The N-terminal 609 amino acids of Bassoon may be targeted to the Golgi apparatus and to synaptic vesicle clusters but are not required for either trafficking step. By contrast, a central region of Bassoon is essential for its anchoring within the CAZ, for synaptic transmission at a certain set of synapses, and for anchoring synaptic ribbons at active zones in retinal photoreceptor cells (17)(18)(19)(20).The modes of CAZ assembly are currently being studied. Fluorescence imaging studies have revealed a stepwise incorporation of mobile units of Bassoon into nascent presynapses (21,22).…”

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confidence: 99%

Assembly of Active Zone Precursor Vesicles

Dresbach

Torres

Wittenmayer

et al. 2006

Journal of Biological Chemistry

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Neurotransmitter release from presynaptic nerve terminals is restricted to specialized areas of the plasma membrane, so-called active zones. Active zones are characterized by a network of cytoplasmic scaffolding proteins involved in active zone generation and synaptic transmission. To analyze the modes of biogenesis of this cytomatrix, we asked how Bassoon and Piccolo, two prototypic active zone cytomatrix molecules, are delivered to nascent synapses. Although these proteins may be transported via vesicles, little is known about the importance of a vesicular pathway and about molecular determinants of cytomatrix molecule trafficking. We found that Bassoon and Piccolo co-localize with markers of the trans-Golgi network in cultured neurons. Impairing vesicle exit from the Golgi complex, either using brefeldin A, recombinant proteins, or a low temperature block, prevented transport of Bassoon out of the soma. Deleting a newly identified Golgi-binding region of Bassoon impaired subcellular targeting of recombinant Bassoon. Overexpressing this region to specifically block Golgi binding of the endogenous protein reduced the concentration of Bassoon at synapses. These results suggest that, during the period of bulk synaptogenesis, a primordial cytomatrix assembles in a trans-Golgi compartment. They further indicate that transport via Golgi-derived vesicles is essential for delivery of cytomatrix proteins to the synapse. Paradigmatically this establishes Golgi transit as an obligatory step for subcellular trafficking of distinct cytoplasmic scaffolding proteins.Synapses of the central nervous system are highly specialized asymmetric cell-cell contact sites mediating communication between neurons. A characteristic feature of synaptic junctions is the deposition of electron-dense meshworks of cytoskeletal and cytoskeleton-associated proteins at the pre-and postsynaptic plasma membrane. On the presynaptic side, this cytoskeletal protein matrix is called cytomatrix assembled at active zones (CAZ) 4 ; it defines the sites where synaptic vesicles dock and fuse to release neurotransmitter (1). The CAZ is thought to mediate pivotal events of synapse formation and function, including spatial restriction of neurotransmitter release to active zones and local recruitment of proteins and organelles (1-4). CAZ-specific proteins include Munc13s, which are essential for neurotransmitter release (5, 6); the Rab3-interacting molecules RIM1␣ and RIM2␣, which are scaffolding proteins regulating presynaptic events (7, 8); the scaffolding protein CAST1/ERC2 (9 -11); and Bassoon and Piccolo/Aczonin. The latter two proteins are related giant CAZ components of 420 and 530 kDa, respectively, present at both excitatory and inhibitory synapses (12-16). The N-terminal 609 amino acids of Bassoon may be targeted to the Golgi apparatus and to synaptic vesicle clusters but are not required for either trafficking step. By contrast, a central region of Bassoon is essential for its anchoring within the CAZ, for synaptic transmission at a certain set of ...

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Molecular dissection of the photoreceptor ribbon synapse

Cited by 361 publications

References 42 publications

Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells

Acetylation by p300 Regulates Nuclear Localization and Function of the Transcriptional Corepressor CtBP2

Assembly of Active Zone Precursor Vesicles

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