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Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex.

tom Dieck S, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtová A, Bracko O, Gundelfinger ED, Brandstätter JH - J. Cell Biol. (2005)

Bottom Line: Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel alpha1 subunit, and ERC2/CAST1.A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex.Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroanatomy, Max Planck Institute for Brain Research, D-60528 Frankfurt/Main, Germany.

ABSTRACT
The ribbon complex of retinal photoreceptor synapses represents a specialization of the cytomatrix at the active zone (CAZ) present at conventional synapses. In mice deficient for the CAZ protein Bassoon, ribbons are not anchored to the presynaptic membrane but float freely in the cytoplasm. Exploiting this phenotype, we dissected the molecular structure of the photoreceptor ribbon complex. Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel alpha1 subunit, and ERC2/CAST1. A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex. Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses.

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Differential localization of CAZ proteins defines two compartments of the photoreceptor ribbon synaptic complex. The ribbon-associated complex of CAZ proteins includes RIBEYE/CtBP2, CtBP1, KIF3A, Piccolo, and RIM1; the plasma membrane/arciform density-associated complex includes RIM2, Munc13-1, ERC2/CAST1, and a Ca2+ channel α1 subunit. Bassoon localizes at the border between the two compartments.
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fig8: Differential localization of CAZ proteins defines two compartments of the photoreceptor ribbon synaptic complex. The ribbon-associated complex of CAZ proteins includes RIBEYE/CtBP2, CtBP1, KIF3A, Piccolo, and RIM1; the plasma membrane/arciform density-associated complex includes RIM2, Munc13-1, ERC2/CAST1, and a Ca2+ channel α1 subunit. Bassoon localizes at the border between the two compartments.

Mentions: In our search for CAZ proteins that potentially interact at the photoreceptor ribbon complex, we were able to dissect a second cytomatrix compartment that is distinct from the plasma membrane/arciform density compartment, the ribbon (Fig. 8). The two compartments are likely to reflect a segregation of CAZ functions at the photoreceptor ribbon synapse. This is most obvious by the differential distribution of RIM1 and RIM2. RIMs, CAZ proteins that function in a late step of exocytosis following the docking of synaptic vesicles, directly and indirectly interact with many proteins implicated in vesicle priming and neurotransmitter release at presynaptic active zones of synapses, including Munc13-1, ERC2/CAST1, and L-type calcium channels (Wang et al., 1997; Schoch et al., 2002; Calakos et al., 2004; Südhof, 2004). Ribbon-associated molecules including RIM1, Piccolo, RIBEYE/CtBP2, and CtBP1 may be involved in tethering synaptic vesicles to the ribbon and in preparing them for exocytosis. In particular, the functions proposed for RIBEYE/CtBP2 and CtBP1 could play a role in this latter process. Both proteins were first characterized as transcriptional corepressors (Turner and Crossley, 2001). In addition, they display homology to NAD+-dependent dehydrogenases and bind NAD+/NADH (Schmitz et al., 2000; Zhang et al., 2002). Most interestingly, in the context of preparing vesicles for exocytosis at the ribbon, they may function as lysophosphatidic acyl-CoA transferases (LPAAT) and thus modulate the curvature of lipid membranes (Kooijman et al., 2003). Indeed, CtBP1 has been implicated in membrane fission processes at the Golgi complex, where it is involved in a fission reaction generating aligned vesicles from continuous tubular structures (Weigert et al., 1999). As shown in this paper, CtBP1 is not only a protein of the photoreceptor ribbon synapse, but also of conventional brain synapses. This suggests a general role for CtBP family members in active zone function. Our results add molecular evidence to the hypothesis that the ribbon has a correlate at the conventional synapse (Zhai and Bellen, 2004).


Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex.

tom Dieck S, Altrock WD, Kessels MM, Qualmann B, Regus H, Brauner D, Fejtová A, Bracko O, Gundelfinger ED, Brandstätter JH - J. Cell Biol. (2005)

Differential localization of CAZ proteins defines two compartments of the photoreceptor ribbon synaptic complex. The ribbon-associated complex of CAZ proteins includes RIBEYE/CtBP2, CtBP1, KIF3A, Piccolo, and RIM1; the plasma membrane/arciform density-associated complex includes RIM2, Munc13-1, ERC2/CAST1, and a Ca2+ channel α1 subunit. Bassoon localizes at the border between the two compartments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171818&req=5

fig8: Differential localization of CAZ proteins defines two compartments of the photoreceptor ribbon synaptic complex. The ribbon-associated complex of CAZ proteins includes RIBEYE/CtBP2, CtBP1, KIF3A, Piccolo, and RIM1; the plasma membrane/arciform density-associated complex includes RIM2, Munc13-1, ERC2/CAST1, and a Ca2+ channel α1 subunit. Bassoon localizes at the border between the two compartments.
Mentions: In our search for CAZ proteins that potentially interact at the photoreceptor ribbon complex, we were able to dissect a second cytomatrix compartment that is distinct from the plasma membrane/arciform density compartment, the ribbon (Fig. 8). The two compartments are likely to reflect a segregation of CAZ functions at the photoreceptor ribbon synapse. This is most obvious by the differential distribution of RIM1 and RIM2. RIMs, CAZ proteins that function in a late step of exocytosis following the docking of synaptic vesicles, directly and indirectly interact with many proteins implicated in vesicle priming and neurotransmitter release at presynaptic active zones of synapses, including Munc13-1, ERC2/CAST1, and L-type calcium channels (Wang et al., 1997; Schoch et al., 2002; Calakos et al., 2004; Südhof, 2004). Ribbon-associated molecules including RIM1, Piccolo, RIBEYE/CtBP2, and CtBP1 may be involved in tethering synaptic vesicles to the ribbon and in preparing them for exocytosis. In particular, the functions proposed for RIBEYE/CtBP2 and CtBP1 could play a role in this latter process. Both proteins were first characterized as transcriptional corepressors (Turner and Crossley, 2001). In addition, they display homology to NAD+-dependent dehydrogenases and bind NAD+/NADH (Schmitz et al., 2000; Zhang et al., 2002). Most interestingly, in the context of preparing vesicles for exocytosis at the ribbon, they may function as lysophosphatidic acyl-CoA transferases (LPAAT) and thus modulate the curvature of lipid membranes (Kooijman et al., 2003). Indeed, CtBP1 has been implicated in membrane fission processes at the Golgi complex, where it is involved in a fission reaction generating aligned vesicles from continuous tubular structures (Weigert et al., 1999). As shown in this paper, CtBP1 is not only a protein of the photoreceptor ribbon synapse, but also of conventional brain synapses. This suggests a general role for CtBP family members in active zone function. Our results add molecular evidence to the hypothesis that the ribbon has a correlate at the conventional synapse (Zhai and Bellen, 2004).

Bottom Line: Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel alpha1 subunit, and ERC2/CAST1.A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex.Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroanatomy, Max Planck Institute for Brain Research, D-60528 Frankfurt/Main, Germany.

ABSTRACT
The ribbon complex of retinal photoreceptor synapses represents a specialization of the cytomatrix at the active zone (CAZ) present at conventional synapses. In mice deficient for the CAZ protein Bassoon, ribbons are not anchored to the presynaptic membrane but float freely in the cytoplasm. Exploiting this phenotype, we dissected the molecular structure of the photoreceptor ribbon complex. Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel alpha1 subunit, and ERC2/CAST1. A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex. Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses.

Show MeSH