Publications (10)34.59 Total impact
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Article: Evidence for synergistic and complementary roles of Bassoon and darkness in organizing the ribbon synapse.
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ABSTRACT: Ribbon synapses are tonically active high-throughput synapses. The performance of the ribbon synapse is accomplished by a specialization of the cytomatrix at the active zone referred to as the synaptic ribbon (SR). Progress in our understanding of the structure-function relationship at the ribbon synapse has come from observations that, in photoreceptors lacking a full-size scaffolding protein Bassoon (BsnΔ(Ex4/5)), dissociation of SRs coincides with perturbed signal transfer. The aim of the present study has been to elaborate the role of Bassoon as a structural organizer of the ribbon synapse and to differentiate it with regard to the ambient lighting conditions. The ultrastructure of retinal ribbon synapses has been compared between wild-type and BsnΔ(Ex4/5) mice adapted to light (low activity) and darkness (high activity). The results obtained suggest that Bassoon and environmental illumination synergistically and complementarily act as organizers of the ribbon synapse. Thus, light-dependent and Bassoon-independent regulation involves initial SR tethering to the membrane and a basic shape transition of ribbon material from spherical to rod-like, since darkness induces these features in BsnΔ(Ex4/5) rod spherules. However, the tight anchorage of the SR via an arciform density and the proper assembly of SRs to the full-sized horseshoe-shaped complex depend on Bassoon, as these steps fail in BsnΔ(Ex4/5) rod spherules.Neuroscience 01/2013; · 3.38 Impact Factor -
Article: Proper synaptic vesicle formation and neuronal network activity critically rely on syndapin I.
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ABSTRACT: Synaptic transmission relies on effective and accurate compensatory endocytosis. F-BAR proteins may serve as membrane curvature sensors and/or inducers and thereby support membrane remodelling processes; yet, their in vivo functions urgently await disclosure. We demonstrate that the F-BAR protein syndapin I is crucial for proper brain function. Syndapin I knockout (KO) mice suffer from seizures, a phenotype consistent with excessive hippocampal network activity. Loss of syndapin I causes defects in presynaptic membrane trafficking processes, which are especially evident under high-capacity retrieval conditions, accumulation of endocytic intermediates, loss of synaptic vesicle (SV) size control, impaired activity-dependent SV retrieval and defective synaptic activity. Detailed molecular analyses demonstrate that syndapin I plays an important role in the recruitment of all dynamin isoforms, central players in vesicle fission reactions, to the membrane. Consistently, syndapin I KO mice share phenotypes with dynamin I KO mice, whereas their seizure phenotype is very reminiscent of fitful mice expressing a mutant dynamin. Thus, syndapin I acts as pivotal membrane anchoring factor for dynamins during regeneration of SVs.The EMBO Journal 09/2011; 30(24):4955-69. · 9.20 Impact Factor -
Article: Phosphodiesterase 10A in the rat pineal gland: localization, daily and seasonal regulation of expression and influence on signal transduction.
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ABSTRACT: The cyclic nucleotide phosphodiesterase 10A (PDE10A) is highly expressed in striatal spiny projection neurons and represents a therapeutic target for the treatment of psychotic symptoms. As reported previously [J Biol Chem 2009; 284:7606-7622], in this study PDE10A was seen to be additionally expressed in the pineal gland where the levels of PDE10A transcript display daily changes. As with the transcript, the amount of PDE10A protein was found to be under daily and seasonal regulation. The observed cyclicity in the amount of PDE10A mRNA persists under constant darkness, is blocked by constant light and is modulated by the lighting regime. It therefore appears to be driven by the master clock in the suprachiasmatic nucleus (SCN). Since adrenergic agonists and dibutyryl-cAMP induce PDE10A mRNA, the in vitro clock-dependent control of Pde10a appears to be mediated via a norepinephrine → β-adrenoceptor → cAMP/protein kinase A signaling pathway. With regard to the physiological role of PDE10A in the pineal gland, the specific PDE10A inhibitor papaverine was seen to enhance the adrenergic stimulation of the second messenger cAMP and cGMP. This indicates that PDE10A downregulates adrenergic cAMP and cGMP signaling by decreasing the half-life of both nucleotides. Consistent with its effect on cAMP, PDE10A inhibition also amplifies adrenergic induction of the cAMP-inducible gene arylalkylamine N-acetyltransferase (Aanat) which codes the rate-limiting enzyme in pineal melatonin formation. The findings of this study suggest that Pde10a expression is under circadian and seasonal regulation and plays a modulatory role in pineal signal transduction and gene expression.Neuroendocrinology 04/2011; 94(2):113-23. · 2.38 Impact Factor -
Article: Phosphodiesterase10A: abundance and circadian regulation in the retina and photoreceptor of the rat.
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ABSTRACT: Phosphodiesterase10A (PDE10A) is a dual specific cyclic nucleotide phosphodiesterase that is specifically enriched in striatum and which has gained attention as a therapeutic target for psychiatric disorders. The present study shows that PDE10A is also highly expressed in retinal neurons including photoreceptors. The levels of PDE10A transcript and protein display daily rhythms which could be seen in preparations of the whole retina. Corresponding changes in PDE10A mRNA were seen in photoreceptors isolated using laser microdissection. This suggests that the expressional control of the photoreceptor Pde10a gene contributes to the observed cyclicity in the amount of retinal PDE10A. The daily rhythmicity in the retinal PDE10A mRNA amount is retained under constant darkness but can be blocked by constant light or modulated by the lighting regime. It therefore appears to be driven by the endogenous retinal clock system which itself is entrained by light. The findings presented place PDE10A in the context of the visual system and suggest a role of PDE10A in the adaptation of cyclic nucleotide signaling to daily changes in light intensity in retinal neurons including photoreceptors.Brain research 02/2011; 1376:42-50. · 2.46 Impact Factor -
Article: Unique clockwork in photoreceptor of rat.
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ABSTRACT: In mammals, the retina contains a clock system that oscillates independently of the master clock in the suprachiasmatic nucleus and allows the retina to anticipate and to adapt to the sustained daily changes in ambient illumination. Using a combination of laser capture micro-dissection and quantitative PCR in the present study, the clockwork of mammalian photoreceptors has been recorded. The transcript amounts of the core clock genes Clock, Bmal1, Period1 (Per1), Per3, Cryptochrome2, and Casein kinase Iε in photoreceptors of rat retina have been found to undergo daily changes. Clock and Bmal1 peak with Per1 and Per3 around dark onset, whereas Casein kinase Iε and Cryptochrome2 peak at night. As shown for Clock, Per1, and Casein kinase Iε, the oscillation of transcript amounts results in daily changes of the protein products. The in-phase oscillation of Clock/Bmal1 with Pers and the rhythmic expression of Casein kinase Iε do not occur in molecular clocks of other tissues including the suprachiasmatic nucleus. Therefore, the findings presented suggest that the photoreceptor clock is unique not only in its position outside the clock hierarchy mastered by the suprachiasmatic nucleus, but also with regard to the intrinsic rhythmic properties of its molecular components.Journal of Neurochemistry 11/2010; 115(3):585-94. · 4.06 Impact Factor -
Article: Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes.
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ABSTRACT: Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13-1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13-1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation.Cell and Tissue Research 08/2008; 333(2):185-95. · 3.11 Impact Factor -
Article: Transcriptome comparison of murine wild-type and synaptophysin-deficient retina reveals complete identity.
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ABSTRACT: Loss of synaptophysin, one of the major synaptic vesicle membrane proteins, is surprisingly well tolerated in knockout mice. To test whether compensatory gene transcription accounts for the apparent lack of functional deficiencies, comparative transcriptome analyses were carried out. The retina was selected as the most suitable tissue since morphological alterations were observed in mutant photoreceptors, most notably a reduction of synaptic vesicles and concomitant increase in clathrin-coated vesicles. Labeled cRNA was prepared in triplicate from retinae of age- and sex-matched wild-type and mutant litter mates and hybridized to high-density microarray chips. Only three differentially expressed RNAs were identified in this way, one of which was synaptophysin. Further validation by quantitative RT-PCR could only corroborate the results for the latter. We therefore conclude that, despite the distinct morphological phenotype, no significant changes in gene expression are detectable in synaptophysin-deficient animals and that therefore compensatory mechanisms are either pre-existent and/or act at the posttranscriptional level.Brain Research 05/2006; 1081(1):53-8. · 2.73 Impact Factor -
Article: Influence of photoperiodic history on clock genes and the circadian pacemaker in the rat retina.
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ABSTRACT: The influence of seasonal lighting conditions on expression of clock genes and the circadian pacemaker was investigated in the rat retina. For this purpose, the 24-h profiles of nine clock genes (bmal1, clock, per1, per2, per3, dec1, dec2, cry1 and cry 2) and the arylalkylamine N-acetyltransferase gene as an indicator of the circadian pacemaker output were compared between light-dark periods of 8 : 16 and 16 : 8 h. The photoperiod influenced the daily patterns of the amount of transcript for per1, per3, dec2 and arylalkylamine N-acetyltransferase. This indicates that photoperiodic information modulates clock gene expression in addition to the circadian pacemaker of the retina. Under constant darkness, photoperiod-dependent changes in the daily profile of the level of transcript persisted for the arylalkylamine N-acetyltransferase gene but not for any of the clock genes. Hence, quantitative expression of each clock gene is influenced by the photoperiod only under the acute light-dark cycle, whereas the pacemaker is capable of storing photoperiodic information from past cycles.European Journal of Neuroscience 02/2006; 23(1):105-11. · 3.63 Impact Factor -
Article: Mouse photoreceptor synaptic ribbons lose and regain material in response to illumination changes.
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ABSTRACT: Abstract Chemical synapses equipped with ribbons are tonically active, high-output synapses. The ribbons may play a role in the trafficking of synaptic vesicles. Recent findings in retinal rod cells of BALB/c mice indicate that ribbons are large and smooth in the dark phase, and, due to the formation and release of protrusions, small during the light phase. As a consequence of these changes, ribbons may traffick fewer vesicles in the light than in the dark phases. The aim of the present study was to find out whether the above ribbon changes in this mouse strain are strictly illumination-dependent and which signalling processes may be involved. Here, we show that ribbons form protrusions and release them into the cytoplasm within 30-60 min after lights on, the reverse occurring within 30 min after lights off. Under constant light or constant dark, no circadian rhythm of synaptic ribbon changes is observed. The illumination-dependence of ribbon structure is supported by in vitro experiments showing that in dark-adapted retinas, light induces the same morphological changes as in vivo. In vitro, the effect of light on the ribbons can be counteracted by cyclic guanosine monophosphate and melatonin. In dark-adapted retinas, light effects can be produced by decreasing the calcium ion concentrations in the incubation media. These results suggest that in retinal rod cells, the well known phototransduction signalling mechanisms may be responsible for the ribbon changes presently and previously reported.European Journal of Neuroscience 04/2004; 19(6):1559-71. · 3.63 Impact Factor -
Article: Untersuchungen zur Plastizität retinaler und pinealer Synaptic Ribbons [microform] /
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ABSTRACT: Mikrofiche-Ausg.: 2 Mikrofiches : 24x. Mainz, Universiẗat, Diss., 1996.
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2004–2013
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Johannes Gutenberg-Universität Mainz
Mainz, Rhineland-Palatinate, Germany
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